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PAN2 binds PAN3. 320 / 327
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"In humans, TNRC6C also independently interacts with the PAN2 and PAN3 complex and contributes to gene silencing by miRNA."
24904636
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"Structural basis for Pan3 binding to Pan2 and its function in mRNA recruitment and deadenylation."
24872509
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"This binding allows Pan3 to supply Pan2 with substrate polyA RNA, facilitating efficient mRNA deadenylation by the intact Pan2 and Pan3 complex."
24872509
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"The mechanism of Pan2 and Pan3 complex formation and substrate binding remain elusive."
24872509
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"Recent work showed that Pan3 forms a homodimer in solution (Christie etal, 2013) raising the question of whether the Pan2 and Pan3 complex contains one or two exonuclease subunits."
24872509
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"The poly (A) tail degrading enzyme Pan2-Pan3 complex has been reported to be inhibited by Pbp1 [ xref ]."
33984024
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"To examine whether the Pan2-Pan3 complex controls COX10 , COX11 , and AIM33 mRNA, we prepared the pbp1Δ pan2Δ double mutant and then performed qRT-PCR analysis."
33984024
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"These results suggest that Pbp1 does not regulate the expression of COX10 , COX11 , and AIM33 mRNAs through the Pan2-Pan3 complex."
33984024
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"From the above results, Pbp1 can stabilize COX10 , COX11 , and AIM33 mRNAs by inhibiting decapping factors rather than acting on deadenylases, the Ccr4-Not and Pan2-Pan3 complexes."
33984024
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"Two other Drosophila poly(A)-specific ribonucleases, the Pan2-Pan3 complex and the poly(A)-specific ribonuclease (PARN), have both specialized and redundant functions when compared to the CCR4-NOT com[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30149007
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"The PAN2 and PAN3 complex is a heteromultimer in which PAN2 is the catalytically active deadenylase subunit XREF_BIBR."
27558897
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"mRNA degradation is generally initiated by poly(A) tail shortening referred to as deadenylation, which is catalyzed by the Ccr4-Not and the Pan2-Pan3 complexes [ xref ]."
30973945
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"Here, we review the three dimensional structures of the ribonuclease complexes (Pan2-Pan3, Ccr4-Not, Xrn1, exosome) and the mRNA decapping enzymes (Dcp2, DcpS) that are involved in mRNA turnover."
37709756
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"In the standard view, poly(A) tails on human mRNAs are initially trimmed by the Pan2-Pan3 complex."
29932908
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"The main deadenylases implicated in the 5′-3′ degradation pathway are the Pan2-Pan3 complex and the multi-subunit Ccr4-Not deadenylase ( xref ; xref ; xref ; xref ; xref )."
37876592
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"Pan2–Pan3 is composed of one Pan2 and two Pan3 molecules ( xref ; xref , xref ; xref )."
32295929
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"In addition, the GW182 (TNRC6) component of the miRNA repression complex has been implicated in mRNA-specific recruitment of Pan2-Pan3 ( xref ; xref )."
37876592
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"Although all the three kinds of deadenylases, Pan2–Pan3, PARN, and Ccr4-Pop2, belong to the DEDD-exoribonuclease superfamily, they are classified into different families."
18430587
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"We show by coimmunoprecipitation and directed two-hybrid studies that the Pan2 and Pan3 proteins physically interact."
8816488
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"The analysis also reveals a functional interaction of the Pan2-Pan3 complex with the Tex1 subunit of the TREX complex (R > 0.55), which is involved in mRNA export ( Strässer et al., 2002 )."
24119399
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"PAN3, in turn, binds to PABPC1 and PAN2 and may act as a bridging factor."
21981923
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"To investigate the molecular mechanism of mRNA deadenylation by Pan2-Pan3, we purified recombinant S.cerevisiae Pan2 and Pan3 complex (scPan2-Pan3) and polyA binding protein Pab1 (XREF_SUPPLEMENTARY)."
24872509
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"In contrast, Pan2 and Pan3 complex containing a catalytic mutation in Pan2 (E912A) did not have nuclease activity (XREF_SUPPLEMENTARY)."
24872509
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"Thus, the purified Pan2 and Pan3 complex is an active deadenylase in vitro and appears to have an intrinsic ability to bind polyA RNA."
24872509
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"The PAN2 and PAN3 complex is involved in an early phase of deadenylation in which long poly (A) tails are shortened to approximately 50-110 nucleotides, depending on the organism (Yamashita et al., 20[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
21981923
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"The PAN2 and PAN3 complex is stimulated by the cytoplasmic poly (A)-binding protein PABPC1 (Boeck et al., 1996; Brown et al., 1996; Uchida et al., 2004)."
21981923
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"To assess whether the zinc finger is the only component in the Pan2 and Pan3 complex that binds directly to RNA, we deleted it from scPan3 and investigated the ability of the truncated scPan2 and Pan3 complex to bind RNA."
24872509
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"Accordingly, PAN3 interacts with PABPC1 and recruits PAN2, the catalytic subunit, to mRNA targets (Brown et al., 1996; Mangus et al., 2004; Siddiqui et al., 2007; Uchida et al., 2004)."
21981923
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"Although PAN2 depletion does not suppress silencing (Behm-Ansmant et al., 2006; Piao et al., 2010), overexpression of a catalytically inactive PAN2 mutant slows down the initial phase of target deaden[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
21981923
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"Additionally, TNRC6C interacted with PAN3, a subunit of the dimeric PAN2 and PAN3 complex, but not with PAN2, which is the catalytically active subunit."
21981923
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"As shown in Fig XREF_FIG C and XREF_SUPPLEMENTARY, ctPan2 alone has greatly reduced activity compared to the Pan2 and Pan3 complex and only removes approximately 30 As in 2h."
24872509
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"These data indicated that a Pan3 dimer might bind two copies of Pan2 with an overall stoichiometry of 2:2."
24872509
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"To establish the stoichiometry of the Pan2 and Pan3 complex, we used non covalent nanoelectrospray ionization mass spectrometry (nanoESI-MS)."
24872509
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"Structural basis of Chaetomium thermophilum Pan2 and Pan3 complex formation."
24872509
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"To understand the basis of subunit association in the Pan2 and Pan3 complex, we determined the crystal structure of the pseudokinase and C-terminal domains of Pan3 alone and when in complex with the Pan3 interaction domain of Pan2."
24872509
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"Together, our data suggest that the role of Pan3 in the Pan2 and Pan3 complex is to supply Pan2 with substrate polyA RNA."
24872509
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"The Pan3 homodimer binds a single Pan2 chain, and the crystal structure of ctPan3 bound to the interacting linker region of ctPan2 (residues 355-406) shows an extensive interface between the two subunits consistent with the integral role of Pan3 in the overall function of the complex."
24872509
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"Because Pan3 is a dimer, there are two zinc fingers and two PAM2 motifs in each Pan2 and Pan3 complex."
24872509
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"A previous study using Pan3 mutants defective in dimerization suggested that a single Pan3 chain could bind Pan2 (Christie etal, 2013)."
24872509
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"In our in vitro deadenylation assay, the Pan2 and Pan3 complex alone completely deadenylates RNA (Fig XREF_FIG C)."
24872509
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"PolyA binding protein stimulates the reaction but is not required, suggesting that this function is intrinsic to the Pan2 and Pan3 complex."
24872509
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"At a molecular level, we propose that the Pan2 and Pan3 complex, probably through RNA recognition by Pan3, can distinguish between the polyA tail and the 3 ' UTR causing a decrease in the deadenylase activity as the polyA tail shortens."
24872509
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"Nevertheless, because both the M2 and C-term regions must be deleted to inhibit binding to deadenylase complexes, we can not rule out that these regions are also required for additional interactions.I[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
21981923
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"PAN3 interacts with the catalytic subunit PAN2 (Mangus et al., 2004)."
21981923
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"Furthermore, these results are consistent with previous observations indicating that the CCR4, CAF1, and NOT complex takes over cytoplasmic deadenylation in the absence of the PAN2 and PAN3 complex (T[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
21981923
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"The deadenylation mechanism may be different in human, where Pan2-Pan3 initiates deadenylation ( Boeck et al., 1996; Yamashita et al., 2005 ), whereas the Ccr4-Not complex degrades most of the pA tail[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
24119399
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"Therefore, we re-examined the contribution of these complexes to the degradation of miRNA targets in Drosophila cells, in which the effect of depleting the PAN2 and PAN3 complex on miRNA target half-l[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
21981923
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"In PAN3 depleted cells, the F-Luc-Nerfin reporter exhibited a half-life of 18 +/- 1 min, which is in agreement with previous studies showing that depletion of the PAN2 and PAN3 complex does not signif[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
21981923
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"The role of the PAN2 and PAN3 complex in silencing was also analyzed by determining the effects of PAN3 and NOT1 depletion on silencing that was mediated directly by tethering the GW182 protein."
21981923
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"As observed for the F-Luc-Par-6 reporter, the increase in F-Luc-5BoxB mRNA abundance correlated with a corresponding increase in F-Luc activity.These results together with previous studies indicate th[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
21981923
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"However, it is still possible that the PAN2 and PAN3 complex may be important for the silencing of a subset of miRNA targets.Thus far, our data indicate that GW182 proteins recruit deadenylase complex[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
21981923
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"The PAN complex (or Pan2 and Pan3 complex) is a highly conserved poly (A)-binding protein dependent poly (A) deadenylase complex that catalyses the initial phase of deadenylation of mRNAs prior to the CCR4 and NOT complex catalysed second phase."
27519690
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"In a recent study, the sharp bending of PABP upon binding to poly(A) was confirmed in the cryo-electron microscopy (cryo-EM) structure of yeast PABP–poly(A) 90 complex-associated Pan2-Pan3 deadenylase ( xref )."
34904669
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"In the first step the PAN2 and PAN3 complex shortens the poly (A) tail to about 50-110 nucleotides, while in the second step deadenylation is catalyzed by the CCR4 and NOT complex XREF_BIBR."
23977167
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"Even though the PAN2 and PAN3 complex binds to the GW182 complex XREF_BIBR, XREF_BIBR and the overexpression of a catalytically inactive PAN2 mutant slows down deadenylation XREF_BIBR, the PAN2 and PAN3 complex is not essential for miRNA mediated deadenylation XREF_BIBR, XREF_BIBR."
23977167
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"New findings include mRNA substrate preferences for the deadenylase complexes Ccr4-Not and Pan2-Pan3 and their putative interaction with the two decapping scavenger proteins that act antagonistically."
24119399
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"Binding of the Pan2 and Pan3 complex requires the interaction of the N- and C-term regions surrounding the RRM [XREF_BIBR, XREF_BIBR]."
29080206
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"PABPC1 [poly (A)-binding protein C1] recruits the PAN2 and PAN3 complex to poly (A) tails through binding PAN3 and stimulating USP52 and PAN2 poly (A) nuclease activity [XREF_BIBR, XREF_BIBR]."
23398456
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"Nonetheless, the mechanism for poly(A) recognition by the conserved deadenylase complexes, Pan2–Pan3 and Ccr4–Not, is poorly understood."
31110294
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"In eukaryotes, deadenylation is primarily carried out by two conserved multi-protein complexes: Pan2–Pan3 and Ccr4–Not xref ."
31110294
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"Pan2–Pan3 is a heterotrimeric complex consisting of two Pan3 subunits and one Pan2 subunit, the latter containing an exonuclease domain xref – xref ."
31110294
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"The PAN2 and PAN3 complex functions in general and microRNA mediated mRNA deadenylation."
24880343
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"To determine the specificity of the Pan2–Pan3 deadenylation complex, we carried out in vitro assays ( xref ) with recombinant proteins on 5′ fluorescently-labeled RNA substrates, which consist of a 3′ UTR-like sequence of 20 non-A nucleotides (20mer) and a downstream 30-nucleotide poly(A) tail with different 3′ termini."
31110294
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"As the first step of mRNA decay, deadenylation is first carried out by the Pan2–Pan3 complex and further digested by the Ccr4-Not complex (for review, see xref )."
26843527
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"We found that 3′ guanosines can strongly inhibit S. cerevisiae and H. sapiens Pan2–Pan3 and S. pombe Ccr4–Not in a fully reconstituted in vitro system ( xref , xref )."
31110294
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"For most mRNAs, shortening of the poly(A) tail is thought to be the first step in mRNA decay and requires the consecutive actions of the Pan2-Pan3 and the Ccr4-Caf1-Tob complexes ( Funakoshi et al., 2[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
29056324
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"Relative to an RNA with only adenosines in the 3′ tail, we found that 3′ guanosines, but not cytosines or uracils, strongly inhibited Saccharomyces cerevisiae and Homo sapiens Pan2–Pan3 ( xref )."
31110294
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"Consistent with an ability to remove non-adenosine nucleotides, Pan2–Pan3 also degraded the upstream 3′ UTR-like sequence."
31110294
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"The Ccr4 complex and the Pan2 and Pan3 complex are the major deadenylases involved in poly (A) shortening (Meyer et al., 2004; Parker and Song, 2004; Tucker et al., 2001; Yamashita et al., 2005) while the Dcp2 and Dcp1 complex is the decapping enzyme in the cytoplasm (Beelman et al., 1996; Dunckley and Parker, 1999; Lykke-Andersen, 2002; Steiger et al., 2003; Van Dijk et al., 2002; Wang et al., 2002b)."
19121818
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"Thus, the wild-type Ccr4–Not complex has a different nucleotide specificity compared to Pan2–Pan3."
31110294
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"Relative to an RNA with only adenosines in the 3′ tail, Pan2 UCH-Exo and Pan2–Pan3 were strongly inhibited when the guanosines were in the -4 and -5 positions ( xref , xref )."
31110294
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"In a biphasic model of deadenylation xref , Pan2–Pan3 removes the distal portion of the poly(A) tail, whereas Ccr4–Not removes adenosines proximal to the 3′ UTR."
31110294
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"We show that uridylation has only a mild effect on both Pan2–Pan3 and Ccr4–Not, suggesting that 3′ uridylation alone may not strongly influence deadenylation."
31110294
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"Within the other major deadenylase complex, Pan2–Pan3, several domains and motifs contribute to poly(A) specificity."
32295929
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"Whereas the Pan2 and Pan3 complex was found to hydrolyse poly (A) in a distributive manner, the carbon catabolite repressor protein 4 (Ccr4)-Negative on TATA (Not) complex hydrolyses poly (A) in a processive manner and is responsible for rapid deadenylation."
21278420
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"We have previously reported that mRNA decay is triggered by translation termination and proposed a model for the initiation of mRNA decay: after translation termination, the termination factors eRF1–eRF3 dissociate from PABP bound to the 3′ poly(A) tail, and in turn, Pan2–Pan3 and Caf1–Ccr4 deadenylases associate with PABP, which leads to the activation of the deadenylases and shortening of the poly(A) tail ( xref , xref )."
30395302
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"Additionally, miRNA can also induce target mRNA deadenylation by Pan2–Pan3 and Ccr4–NOT and the subsequent decapping by Dcp1–Dcp2."
23467123
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"Tail removal occurs through the hydrolytic activities of the Pan2-Pan3 deadenylase complex and the multi-functional Ccr4–Not complex [ 25 , 26 , 27 ] ( Figures 2 a and b, 3 b)."
31869589
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"The Pan2-Pan3 complex has a complicated relationship with the poly-A-binding protein Pab1 which both protects the tail but can also trigger tail trimming by the complex ( Figures 2 a, 3 b)."
31869589
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"How the Pan2-Pan3 complex switches between those states, and also how it focuses degradation on just the poly-A tail and not the rest of the transcript has been illuminated by the cryo-EM structure of[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
31869589
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"These data reveal that the oligomeric structure of the RNA-binding domains of Pab1 acts as a molecular ruler that matches a defined surface of the Pan2-Pan3 complex."
31869589
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"It is not only thought to facilitate interactions between the 5′ and 3′ ends of mRNP molecules (via its interaction with eIF4G; 20,21) but is also believed to modulate deadenylation via its interactions with the Pan2‐Pan3 complex xref ."
31520451
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"Deadenylation is performed by the Pan2–Pan3 and Ccr4–Not complexes that contain highly conserved exonuclease enzymes Pan2, and Ccr4 and Caf1, respectively."
32295929
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"In eukaryotes, deadenylation is primarily performed by two highly conserved multiprotein complexes, Pan2–Pan3 and Ccr4–Not, that shorten the poly(A) tail in a 3’–5’ direction."
32295929
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"The novel t (7; 13) (p14; q12)/PAN3-PSMA2 in the neoplastic bone marrow cells could affect two key protein complex : (a) the PAN2 and PAN3 complex (PAN3 rearrangement) which is responsible for deadenylation, the process of removing the poly (A) tail from RNA, and (b) the proteasome (PSMA2 rearrangement) which is responsible for degradation of intracellular proteins."
29560286
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"The Pan3 subunit binds to the carboxy-terminal domain of cytoplasmic poly(A)-binding protein via a polypeptide stretch known as the PABP-interacting motif 2 (PAM2 motif), thereby recruiting the Pan2–Pan3 complex to the poly(A) tail ( xref )."
32295929
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"To determine the nucleotide specificities of the DEDD exonucleases Caf1 and Pan2, we used in vitro biochemical assays with recombinant Pan2–Pan3 or with Ccr4–Not containing a catalytic mutant of Ccr4 (such that Caf1 was the only active nuclease) ( xref )."
32295929
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"Here, the Pan2–Pan3 and Ccr4–Not complexes are responsible for polyA shortening with the latter playing the decisive role in the recruitment and activation of the decapping machinery [ xref , xref ]."
39921564
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"The lack of inhibitory effect by uracils on Pan2–Pan3 and Ccr4–Not suggests that the oligo(U) tail alone does not impede deadenylation ( xref )."
32295929
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"In contrast, the presence of guanosines within the poly(A) tail inhibits both Pan2–Pan3 and Ccr4–Not ( xref )."
32295929
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"In the case of the PAN2 and PAN3 complex, both Pan2 and Pan3 were more highly expressed in the carcass group (XREF_FIG E)."
33376967
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"PAN3 codes for the regulatory subunit of the poly (A)-nuclease (PAN) deadenylation complex (PAN2 and PAN3 complex), one of two cytoplasmic eukaryotic poly (A) nuclease complexes involved in mRNA decay [XREF_BIBR]."
29560286
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"The PAN2 and PAN3 complex specifically shortens poly (A) tails of RNA when the poly (A) stretch is bound by poly (A)-binding protein (PABP), followed by rapid degradation of the shortened mRNA tails by the CCR4 and NOT complex [XREF_BIBR, XREF_BIBR]."
29560286
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"Such differences would be expected if miRNAs preferentially direct the deadenylation of shorter tails, as might be inferred from reports that (1) miRNA function depends more on recruitment of the CCR4-NOT deadenylase complex than it does on recruitment of the PAN2-PAN3 deadenylase complex, and (2) the CCR4-NOT deadenylase complex acts at a later, more processive step of mRNA deadenylation than does the PAN2 and PAN3 complex."
31902668
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"The PAN3 N-term region contains a canonical PAM2 motif and interacts with PABPC1, whereas the C-term kinase like domain is required for PAN3 binding to PAN2, the catalytic subunit of the PAN2-PAN3 deadenylase complex."
22402495
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"Two cytoplasmic deadenylation complexes degrade the poly (A) tail : first the PAN2 and PAN3 complex shortens the 3 ' poly (A) tail to approximately 100 nt that are then trimmed by the TOB, CAF1, CCR4, and NOT complex [XREF_BIBR]."
29899850
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"In contrast, tethered PAN3 did not repress reporter expression (XREF_SUPPLEMENTARY), suggesting that the PAN2 and PAN3 complex can not repress translation in the absence of deadenylation."
23463101
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"To date, three types of deadenylase have been identified in mammals, including the CCR4 and NOT complex, the PAN2 and PAN3 complex, and PARN."
33104214
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"Yeast cells have two major cytoplasmics deadenylase complexes, Ccr4-Not and Pan2-Pan3 [ 1–4 ]."
34280615
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"The Pan2-Pan3 complex comprises the catalytic subunit Pan2, a member of the RNase D family, and the regulatory subunit Pan3 [ 5 ]."
34280615
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"We have also shown that LRG1 poly(A) tail in ccr4Δ mutant is longer than that in WT cell and shorter than that in ccr4Δ pan2Δ cell in the stationary phase [ 8 ], suggesting that Pan2-Pan3 complexes to[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
34280615
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"Up to date, many studies have mainly focused on the Ccr4-Not complex whereas only few studies have focused on Pan2-Pan3 complex or on the interplay between these two complexes."
34280615
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"Our results suggest that the Pan2-Pan3 complex has important roles in the growth on non-fermentable carbon sources in coordination with the Ccr4-Not complex."
34280615
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"We also observed that the ccr4Δ pan3Δ double mutant could not grow on YPGlyLac media ( Fig. S2B ), indicating that the Pan2-Pan3 complex regulates cell growth in YPGlyLac media."
34280615
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"Since Pan2-Pan3 complex is required for cell growth on YPGlyLac media in the absence of Ccr4, Pan2-Pan3 might have an important role for growth in non-fermentable carbon source."
34280615
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"These results suggest that Pan2-Pan3 and Ccr4-Not complexes were not involved in the regulation of expression of the genes that function in gluconeogenesis and mitochondria."
34280615
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"Pbp1 is supposed to negatively regulate the Pan2 and Pan3 complex, another cytoplasmic deadenylase, which contributes to regulation of mRNA poly (A) tail length [XREF_BIBR, XREF_BIBR]."
28231297
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"It is thought that the Pan2 and Pan3 complex act as primary deadenylase [XREF_BIBR]; however, here we found that this complex could also act as secondary cytoplasmic deadenylase in the absence of both Ccr4 and Pbp1 in the stationary phase."
28231297
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"Taken together, we first described here that Pbp1 together with the Pan2 and Pan3 complex contributes to the regulation of poly (A) tail length in the stationary phase in vivo through a particular example, LRG1 poly (A) tail."
28231297
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"A recent cryoEM structure of the yeast Pan2-Pan3 complex provides an explanation for why it preferentially acts on the distal (not the proximal) poly(A) tail xref ."
34594027
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"Furthermore, we found that Pbp1 together with the Pan2 and Pan3 complex regulates LRG1 poly (A) tail in vivo."
28231297
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"XREF_BIBR, XREF_BIBR The PAN2 and PAN3 complex is involved in the early phase of deadenylation and shortens mRNA poly (A) tails in a distributive manner."
23303381
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"XREF_BIBR, XREF_BIBR The CCR4 and NOT complex is sufficient for mRNA deadenylation in the absence of the PAN2 and PAN3 complex."
23303381
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"These results are consistent with previous findings that Pan3 is a genuine PABP binding protein and that Pan2 and Pan3 can form complexes in vivo."
18625844
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"Pan2-Pan3 has an intrinsic affinity for cytoplasmic poly(A)-binding protein (PABPC) and prefers long poly(A)-PABPC ribonucleoprotein particles (RNPs)."
37876592
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"Mammalian deadenylation exhibits biphasic kinetics, with the Pan2–Pan3 and Ccr4–Caf1 deadenylase complexes mediating the first and second phase, respectively; however, the significance of the biphasic nature of deadenylation in mRNA turnover remains unclear."
28559491
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"In the first phase, the 3′ poly(A) tails are shortened to ∼110–150 nt by the Pan2–Pan3 complex, where Pan2 is the catalytic subunit and Pan3 is the regulatory factor."
28559491
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"Deadenylation: the Pan2-Pan3 complex."
37876592
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"The observations that the miRNA–RISC complex accelerates deadenylation by recruiting both the Pan2–Pan3 and Ccr4–Caf1 deadenylase complexes ( xref ; xref ; xref ; xref ) further underscore the importance of the two-pronged deadenylation in mRNA metabolism."
28559491
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"The Pan2-Pan3 deadenylase is one of two deadenylase complexes implicated in the initiation of the 5’-3’ decay of mRNA by Xrn1."
37876592
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"Previous studies using individual reporter mRNAs showed that compromising Pan2–Pan3 deadenylase activity only modestly affects deadenylation ( xref ; xref ; xref ; xref ; xref ), suggesting that Ccr4–Caf1–Not complex may play a major role in eukaryotic mRNA deadenylation ( xref ; xref )."
28559491
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"This raised a critical issue concerning the functional significance of the first-phase deadenylation and the involvement of the Pan2–Pan3 complex in mRNA metabolism."
28559491
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"Several recent structural and in vitro studies also provided new insight into the organization of Pan2–Pan3 complex and support a pivotal role for Pan3 as the regulatory subunit of the complex ( xref ; xref ; xref ; xref )."
28559491
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"The Pan2-Pan3 complex is highly conserved ( xref ; xref ) with an atypical architecture in which an asymmetric Pan3 homodimer is bound by a single Pan2 subunit (Pan2:Pan3 = 1:2) ( xref ; xref ; xref )."
37876592
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"Considering that (i) NOT1 interacts with NOT2 [reviewed in], (b) the PAN2 and PAN3 complex interacts with PABP and (c) the CCR4-NOT and PAN2-PAN3 complexes form a larger multiprotein complex in vivo, our observations indicate a high degree of connectivity and redundancy within the GW182 interaction network, which could explain why mutations in individual motifs do not abolish partner binding or silencing activity, but a combination of two or more mutations is required to abrogate binding and silencing activity."
23172285
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"Pan3 forms an asymmetric homodimer when assembled into the yeast Pan2-Pan3 complex ( xref ; xref ; xref ; xref )."
37876592
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"We previously reported the mechanism of mRNA deadenylation, in which the translation termination factor eRF3 and two major cytoplasmic deadenylase complexes, Pan2–Pan3 and Caf1–Ccr4–Tob, play central [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
25446091
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"Moreover, the ability for nucleotide binding seems required for the ribonuclease activity of the Pan2-Pan3 complex ( xref )."
37876592
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"In contrast, truncating either the C-terminal domain or the pseudokinase domain abolished the interaction of Pan3 with Pan2 ( xref C;; ΔC or ΔK)."
28559491
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"These results demonstrate that both pseudokinase and C-terminal domains are necessary for Pan2–Pan3 interaction and that these two Pan3 domains together are sufficient to interact with Pan2."
28559491
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"Moreover, the observation that the Pan3 ΔN mutant pulls down less Pan2 than the WT Pan3 does in BEAS-2B cells () indicates that the N-terminal domain of Pan3, albeit not required for Pan2-binding, can also influence the Pan3–Pan2 interaction."
28559491
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"Together, we conclude that Pan3L and Pan3S have distinct effects on Pan2 deadenylase activity and that both Pan3–PABP and Pan3–Pan2 interactions are critical for regulating the Pan2-mediated deadenylation in vivo."
28559491
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"Previously, we have shown that compromising the Pan2–Pan3 deadenylase activity impedes the rapid decay of a nonsense-codon containing mRNA ( xref ; xref )."
28559491
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"The Pan3 homodimer binds a single Pan2 subunit via the N-terminal WD40 domain and the PID linker of Pan2 ( xref ; xref ; xref )."
37876592
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"However, even though Pan2-Pan3 nuclease activity is stimulated by the presence of PABPC, removal of the PAM2 motif of Pan3 has moderate effect on the activity of the Pan2-Pan3 complex when short oligo(A) substrates are used in vitro ( xref ; xref )."
37876592
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"Mammalian deadenylation exhibits biphasic kinetics with Pan2–Pan3 and Ccr4–Caf1 deadenylase complexes mediating the first and second phases, respectively ( xref )."
28559491
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"However, nuclease activity of Pan2-Pan3 is markedly increased in the presence of long poly(A) substrates containing 70 or 90 nucleotides that can accommodate two or three PABPC subunits ( xref )."
37876592
sparser
"The Pan2-Pan3 complex recognises a RNP containing a 90-mer poly(A) bound to three PABPC molecules through two main interactions ( xref )."
37876592
sparser
"Previous studies using individual reporter mRNAs showed that compromising Pan2–Pan3 deadenylase activity only modestly affects deadenylation ( xref ; xref ; xref ; xref ; xref ), raising the critical issues concerning the functional significance of the first-phase deadenylation and the involvement of the Pan2–Pan3 complex in mRNA metabolism."
28559491
reach
"The Pan2 and Pan3 complex, which is responsible for the first step (i.e., shortening the poly (A) tail to 110 nt), is evolutionarily conserved; however, its function in deadenylation appears to be dispensable."
21957004
sparser
"Through interaction between Pan3S and PABP, Pan2–Pan3 forms a complex with PABP associated with the mRNA 3′ poly(A) tail."
28559491
sparser
"In summary, the present results provide new mechanistic insights into the biphasic deadenylation process and further elaborate the functional impacts of the Pan2–Pan3 complex in mRNA deadenylation and degradation in mammalian cells."
28559491
sparser
"Previous studies have identified deadenylase complexes Caf1–Ccr4 and Pan2–Pan3 in PBs, highlighting the significance of deadenylation for PB formation ( xref )."
38869059
sparser
"Deadenylation by Pan2-Pan3 and Ccr4-Not result in the specific recognition of oligoadenylated mRNA by the Lsm1-7-Pat1 complex."
37876592
sparser
"In recent years, a large body of work has established critical steps in the 5′-3′ degradation pathway, including the molecular basis of the catalytic steps required for deadenylation by Pan2-Pan3, decapping, and degradation of the RNA body by Xrn1."
37876592
sparser
"It was reported that nonstop mRNA is rapidly degraded from 3′ end, and neither the Pan2–Pan3 nor the Ccr4-Not complex are not involved in this quality control system [6] ."
23416749
reach
"Deadenylation takes place in two successive steps involving, firstly, the PAN2 and PAN3 complex (poly (A) nuclease 2 and 3) and, secondly, the CAF1, CCR4, and NOT complex or the deadenylation complex PARN (poly (A)-specific ribonuclease) [XREF_BIBR]."
29495341
reach
"Given the profound effect of HDACi on mRNA deadenylation and decay, it is well possible that other deadenylases such as the PAN2 and PAN3 complex, which acts early in deadenylation (Schwede et al., 20[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
27635759
sparser
"In the cytoplasm, exonuclease-mediated mRNA decay begins by first removing the poly A tail by one of the deadenylase complexes (CCR4-NOT complex, Pan2-Pan3, PARN)."
32659634
sparser
"Usp5 promotes Brat-mediated localization and segregation of scaffolding components of the CCR4-Not1 and Pan2-Pan3 deadenylase complexes in the basal cortex of mitotic neuroblasts."
39739530
sparser
"The current model for general mRNA decay in yeast involves biphasic poly(A) tail shortening by Pan2-Pan3 and Ccr4-Not deadenylase complexes, decapping by the Dcp1/Dcp2 holoenzyme, and exonucleolytic Xrn1-mediated 5’-3’ degradation or exosome-mediated 3’-5’ degradation [ xref , xref , xref ]."
39236083
sparser
"On the one hand, PABPC1/Pab1 stimulates deadenylation by recruiting Pan2-Pan3 to the poly(A) tail through its interaction with the PAM2 motif on Pan3 [ xref , xref , xref , xref , xref ]."
39236083
sparser
"In this review, we will focus on the main cytoplasmic deadenylases: the Pan2–Pan3 complex and the multisubunit Ccr4–Not complex."
23337855
reach
"Deadenylation in yeast is carried out by the Pan2 and Pan3 complex as well as the by Ccr4, Pop2, and Not complex."
22785621
sparser
"With its C-terminal region, Pan3 interacts tightly with Pan2 [66,69] ."
23337855
sparser
"Binding of the Pan2–Pan3 complex requires the interaction of the N- and C-term regions surrounding the RRM [ xref , xref ]."
29080206
sparser
"However, co-immunoprecipitation analysis indicated that PAN3 was physically associated with USP52 as reported xref , xref , but not with ASF1A (Fig.  xref )."
29599486
sparser
"While the interplay between Pan2-Pan3 and Ccr4-Not is not fully understood, it is clear that their concerted action is often the rate-limiting step for mRNA decay ( Cao and Parker, 2001 ) and a focal [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
22959269
sparser
"These factors recruit the core mRNA degradation machinery that carries out the following steps: i) shortening of the poly(A) tail by the Ccr4-Not and Pan2-Pan3 poly (A)-specific nucleases (deadenylases); ii) removal of the 5′cap structure by the Dcp1-Dcp2 decapping complex that is recruited by the Lsm1-7-Pat1 complex; and iii) degradation of the mRNA body by the 5′-3′ exoribonuclease Xrn1."
37876592
sparser
"While the Pan2-Pan3 deadenylase may primarily be involved in general deadenylation, degradation of a target mRNA appears to be mainly regulated by recruitment of the Ccr4-Not complex by factors binding in the 3′UTR of the messenger (reviewed in xref ; xref ; xref )."
37876592
sparser
"In contrast, PARN, a homodimeric deadenylase that also contains a cap-binding domain, and Pan2, which forms a heterodimeric complex with Pan3, contain a DEDD domain ( xref , xref , xref )."
24170810
reach
"Although Pan3 and Caf1 associate with Pan2 and Ccr4 poly (A) nucleases, respectively, their in vivo roles in mammalian mRNA turnover remain unclear."
18625844
reach
"Although Pan2 and Pan3 can form a complex in the cytoplasm, the finding that HA-Pan3 can be detected in P-bodies when it is overexpressed alone (XREF_FIG) suggests that Pan3 can associate with P-bodies without a coordinated expression of Pan2."
18625844
sparser
"In agreement with their role in cytoplasmic mRNA deadenylation, both Ccr4–Not and Pan2–Pan3 are predominantly localised in the cytoplasm [19,83,84] ."
23337855
sparser
"Analysis of yeast pan2Δ and pan3Δ strains confirms the role of the Pan2–Pan3 dimer in mRNA deadenylation."
23337855
sparser
"Based on these observations, it was proposed that shortening of the poly(A) tail by the Pan2–Pan3 deadenylase is rapid and may represent the initial phase of deadenylation, with deadenylation of the r[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
23337855
sparser
"Similar to yeast, the role of the Pan2–Pan3 nuclease is also of secondary importance in Drosophila Schneider cells [89] ."
23337855
sparser
"In human cells, the role of Pan2–Pan3 and Ccr4–Not was investigated by transcriptional pulse experiments based on an inducible promoter system."
23337855
sparser
"Combined with siRNA-mediated knockdown or over-expression of (inactive) catalytic subunits, it was shown that the early phase is mainly carried out by Pan2–Pan3, whereas both catalytic subunits of Ccr[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
23337855
sparser
"Several findings suggest extensive redundancy between the Ccr4–Not and Pan2–Pan3 complexes in deadenylation of cytoplasmic mRNA."
23337855
sparser
"A simple explanation for these observations is to assume that Pan2–Pan3 can largely compensate for loss of Ccr4–Not activity and vice versa."
23337855
sparser
"Deadenylation of transcripts is the first step in mRNA decay. xref , xref We tested whether Usp5 promotes the recruitment of the Pan2-Pan3 and CCR4-Not1 deadenylases to the Brat complex."
39739530
sparser
"We reconstituted this process in vitro using recombinant proteins and show that Pan2-Pan3 associates with and degrades poly(A) RNPs containing two or more Pab1 molecules."
31104843
sparser
"We assessed the binding of Pan2-Pan3 by size exclusion chromatography (SEC) using a catalytically inactive version of the deadenylase complex that we had previously characterized (Pan2 Asp1020Ala mutant, Pan2cat; xref )."
31104843
sparser
"Both the Pan2–Pan3 and Ccr4–Not complexes can be recruited by two independent mechanisms."
23337855
sparser
"This conformation appears to be dictated by two properties: the presence of a flexible joint at the RRM3 domain and the relative position of the interacting Pan2-Pan3 surfaces."
31104843
sparser
"Once a single Pab1 is left, the poly(A) RNP is inefficiently bound and deadenylated by Pan2-Pan3."
31104843
sparser
"During termination of translation, it has been reported that a series of coupled events centred around PABPC1 results in the consecutive recruitment of translation release factor eRF1–eRF3, followed b[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
23337855
sparser
"These results suggest that scaffolding components of Pan2-Pan3 and CCR4-Not1 deadenylases might be in a complex with Brat and Usp5 in mitotic neuroblasts."
39739530
sparser
"By contrast, little is presently known about specific mechanisms of Pan2–Pan3 recruitment involving RNA-binding proteins."
23337855
sparser
"Neither does knockdown of pan2 , which encodes the enzymatic subunit of the Pan2-Pan3 deadenylase complex ( xref )."
37053289
reach
"Lastly, PABPC1 also plays an important role in RNA homeostasis, in that it protects the 3 '-poly (A) tail until proper signals cause it to dissociate and allow deadenylases (e.g., CAF1, CCR4, and NOT complex, PAN2 and PAN3 complex) to initiate the degradation of the mRNA."
29359180
sparser
"MiRNA-mediated deadenylation and the role of the human Ccr4–Not complex were initially described in Drosophila , and shown to be conserved in human cells also identifying a role for Pan2–Pan3 [117–121[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
23337855
sparser
"No mouse models illuminating the role of the Pan2–Pan3 complex have been described to date."
23337855
sparser
"Poly(A) shortening is catalyzed by the Pan2-Pan3 deadenylation complex, preceding both 3′ → 5′ and 5′ → 3′ degradation."
35912117
reach
"In yeast, Saccharomyces cerevisiae, two major deadenylase complexes have been found; the mega-Dalton Ccr4 and NOT complex, which contains two active 3 '-5' exonucleases, Ccr4p and Pop2p, and the heterodimeric Pan2 and Pan3 complex."
21965533
reach
"Deadenylation is generally the rate limiting event in the cytoplasmic mRNA degradation and is catalyzed by the PAN2 and PAN3 complex followed by the CCR4 and NOT complex [XREF_BIBR, XREF_BIBR]."
26078976
reach
"XREF_BIBR It has been proposed that deadenylation proceeds in two steps : the PAN2 and PAN3 complex first degrades the 3 ' end of the poly (A) tail leaving ~ 100 adenosine residues that are then degraded by the TOB, CAF1, and CCR4 complex."
26818177
sparser
"In yeast and mammalian cells, deadenylation begins with the Pan2-Pan3 complex ( Boeck et al., 1996 ; Brown and Sachs, 1998 ; Yamashita et al., 2005 ) and continues with the Ccr4-Not complex ( Daugeron[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
22959269
sparser
"Deadenylation is generally mediated by two major deadenylase complexes, Pan2–Pan3 and Caf1–Ccr4 [9] ."
25446091
sparser
"The Pan2–Pan3 complex consists of catalytic subunit Pan2 and regulatory subunit Pan3 [10] , and both the Caf1 and Ccr4 subunits exhibit the catalytic activity of deadenylase [11–13] ."
25446091
sparser
"Studies in yeast have shown that neither the Pan2-Pan3 nor the Ccr4-Not deadenylase activities are essential in vivo ( Malvar et al., 1992 ; Boeck et al., 1996 ; Brown et al., 1996 )."
22959269
reach
"Whilst the Ccr4 and Not complex is described as the main deadenylase in a variety of organisms, including Saccharomyces cerevisiae and human cells, it is clear that other deadenylase complexes, notably the Pan2 and Pan3 complex, also play an important role."
24391663
reach
"To this extent, three major deadenylation complexes have been reported in vertebrates, the Ccr4, Caf1, and Not complex, the Pan2 and Pan3 complex, and the poly A specific ribonuclease (PARN) complex [XREF_BIBR - XREF_BIBR]."
21278925
reach
"Of particular interest was pan3Delta, which encodes a subunit of the Pan2 and Pan3 complex."
25375137
reach
"Vertebrates express at least three deadenylation complexes : the Ccr4, Caf1, and Not complex, the Pan2 and Pan3 complex, and the poly A specific ribonuclease (PARN) complex [XREF_BIBR, XREF_BIBR, XREF_BIBR]."
23428348
sparser
"We previously proposed a mechanism of mRNA deadenylation, in which the termination factor eRF3 dissociates from the poly(A)-binding protein PABPC1 after the termination of translation, and in turn, th[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
25446091
sparser
"The cluster analysis also reveals differences between the two mRNA deadenylase complexes Ccr4-Not and Pan2-Pan3."
24119399
sparser
"Pab1 can recruit or activate the deadenylases Pan2-Pan3 and the Ccr4 subunit of the Ccr4-Not complex, which cooperate in shortening the pA tail, thought to be a prerequisite for degradation of the transcript ( xref , xref )."
38903079
sparser
"We also investigated how deadenylases Ccr4 and Pan2-Pan3 affected the formation of P-bodies."
28031482
reach
"These include the conserved, trimeric Pan2 and Pan3 complex, composed of a single Pan2 catalytic subunit bound to a Pan3 dimer, the PARN deadenylase, which is absent in single cellular eukaryotes, and less-well characterized enzymes, such as the circadian deadenylase Nocturnin, and the Caf1z and Ccr4d complex."
24391663
sparser
"There are two main deadenylases involved in this step: the Pan2-Pan3 complex that may complete initial, fast deadenylation, while the Ccr4-Not complex may be engaged in the second, slower phase ( xref )."
37152278
reach
"Finally, an important mechanism for the recruitment of both Ccr4-Not and the Pan2 and Pan3 complex to specific mRNAs involves interactions with GW182 and TNRC6 proteins, which are part of the miRNA repression complex."
24391663
reach
"In the case of the Pan2 and Pan3 complex, this is mediated by the presence of a short PAM2 motif in the Pan3 protein, which can interact directly with the PABP C-terminal domain."
24391663
reach
"Thus, where the Pan2 and Pan3 complex can interact directly with the PABP, this interaction is indirect in case of the Ccr4 and Not complex."
24391663
sparser
"These results demonstrate that the Caf1–Ccr4–Tob complex, but not the Pan2–Pan3 complex, is responsible for c-myc mRNA deadenylation."
25446091
sparser
"We concluded that of the fission yeast deadenylases, neither Ccr4 nor Pan2–Pan3 had a large impact on P-body assembly."
28031482
reach
"Deadenylation is triggered by deadenylases, which include the CCR4 and NOT complex, the PAN2 and PAN3 complex and PARN in mammals."
27558897
sparser
"Funakoshi et al. (2007) have demonstrated the eukaryotic elongation factor (eRF3) to work in concert with PABPC1 and the deadenylation complexes Pan2-Pan3 and Caf1-Ccr4 [ xref ] in a sequence-specific manner [ xref ]."
39858595
reach
"The Pan3 subunit binds to the carboxy-terminal domain of cytoplasmic poly (A)-binding protein via a polypeptide stretch known as the PABP interacting motif 2 (PAM2 motif), thereby recruiting the Pan2 and Pan3 complex to the poly (A) tail."
32295929
sparser
"Pbp1 regulates the Pan2-Pan3 deadenylase complex, thereby modulating the mRNA stability and translation efficiency."
33984024
sparser
"COX10 , COX11 , and AIM33 mRNA are not regulated by Pbp1 via the Pan2-Pan3 complex and the Ccr4-Not complex."
33984024
sparser
"Pbp1 has been shown to block the deadenylation mediated by the Pan2-Pan3 complex in terms of poly(A) tail regulation and suppress the growth defect of the ccr4∆ and pop2∆, indicating the Pbp1 plays im[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
38479232
sparser
"From our screen, we found that reducing the dosage of genes encoding the core components of the CCR4–NOT or Pan2–Pan3 complex also enhanced the supernumerary neuroblast phenotype in brat hypomorphic brains ( xref G;)."
30463902
reach
"This deadenylation is carried out by the Pan2 and Pan3 complex as well as by the Ccr4 and Not complex."
27704052
reach
"The Pan2 and Pan3 complex, in which Pan2 carries the catalytic activity, does act in general mRNA decay, but its specific role is not entirely clear."
24904643
reach
"In most published studies that we are aware of, the Pan2 and Pan3 complex was found to act on the same RNAs as the CCR4 and NOT complex, but less efficiently."
24904643
reach
"The fission yeast genome encodes two additional presumptive deadenylases, namely the Pan2 and Pan3 complex and PARN."
19430462
reach
"The Pan2 and Pan3 complex is widely conserved among eukaryotes."
19430462
reach
"Taken together, these data demonstrate that Cid1 and Ccr4, but neither the Pan2 and Pan3 complex nor PARN, are important for mRNA decay, as judged by the increased stability of urg1 transcripts in the corresponding deletion strains."
19430462
reach
"Accordingly, other deadenylases, such as the Pan2 and Pan3 complex or PARN, may be able to act redundantly with Cid1 and the Ccr4 and Caf1 complex, as has been suggested in both budding yeast and human cells XREF_BIBR, XREF_BIBR."
19430462
reach
"Additionally, we also examined ETS1 and ITS1 expression in a catalytic mutant (pan2 Delta) of the Pan2 and Pan3 complex which is an additional mRNA deadenylase complex that is partially redundant with Ccr4-Not [XREF_BIBR]."
25815716
reach
"It may be that the S. pombe Pan2 and Pan3 complex has a role in nuclear trimming of poly (A) tails, as has been shown in budding yeast XREF_BIBR, XREF_BIBR, rather than a role in mRNA decay, as is the case in higher eukaryotes XREF_BIBR, XREF_BIBR, though this would not explain the observed increase in mRNA uridylation in pan2increment and pan3increment cells (XREF_FIG)."
19430462
sparser
"Since Pan2-Pan3 recognizes the Pab1 oligomerization interface, it preferentially acts on poly(A) RNA that is long enough to accommodate multiple Pab1 molecules."
34594027
reach
"Progressive deadenylation (by the Ccr4-Not or Pan2 and Pan3 complexes in yeast or PARN and PAN2 and PAN3 in metazoans) leads to loss of associated poly (A)-binding protein (PABP) [XREF_BIBR, XREF_BIBR] and subsequently to complete exonucleolytic digestion that proceeds either 5 ' to 3 ', and is decapping dependent, or 3 ' to 5 ', and is decapping independent [XREF_BIBR, XREF_BIBR]."
24091060
reach
"Three main poly (A)-specific 3 ' exonucleases, or deadenylases, are known : the poly (A)-specific ribonuclease, the Pan2 and Pan3 complex, and the CCR4 and NOT complex."
24904643
reach
"POP2, like PARN and PAN2, the catalytic subunit of the Pan2 and Pan3 complex, is a member of the DEDD nuclease family."
24904643
reach
"As the deadenylation process generally occurs in a biphasic manner in mammals, in which long poly (A) tails are first gradually shortened by the PAN2 and PAN3 complex to ~ 100nt, followed by the CCR4, CAF1, and NOT complex to 8-12nt XREF_BIBR, it is possible that multiple deadenylases act on the same mRNA with discrete but overlapping functions."
26586468
sparser
"Furthermore, Pan2-Pan3 and Ccr4/Not can create a super complex, which offers a chance to synchronize the two deadenylation processes."
38479232
sparser
"The first step of the RNA decay process is shortening the poly(A) tails of target mRNAs or deadenylation, which is catalyzed by the evolutionarily conserved CCR4–NOT and Pan2–Pan3 deadenylase complexes ( xref ; xref ; xref )."
30463902
sparser
"The recent structure of Pan2-Pan3 bound to a Pab1-poly(A) RNP combined with the earlier structure of Pab1 RRMs 1 and 2 provides important new insight into the overall arrangement of Pab1 on poly(A) RNA xref , xref ."
34594027
reach
"Dissection of the specific roles of the Pan2 and Pan3 complex and PARN is currently being pursued."
19430462
reach
"Mammalian mRNA decay utilizes three major deadenylation complexes, the Ccr4/Caf1/Not (Caf1) complex, the poly A specific ribonuclease (PARN) complex, and the Pan2 and Pan3 complex."
22201737
reach
"However, the exact impact of deadenylation by the PAN2 and PAN3 complex on mRNA expression is poorly understood and the deletion of the corresponding genes in yeast has low influence on growth and poly (A) tail length XREF_BIBR XREF_BIBR."
26912148
sparser
"The current model for general mRNA decay in yeast involves biphasic poly(A) tailing shortening by Pan2-Pan3 and Ccr4-Not deadenylase complexes, decapping by the Dcp1/Dcp2 holoenzyme, and exonucleolytic Xrn1-mediated 5’-3’ degradation or exosome-mediated 3’-5’ degradation [ xref , xref , xref ]."
37398227
sparser
"On the one hand, PABPC1/Pab1 stimulates deadenylation by recruiting Pan2-Pan3 to the poly(A) tail through its interaction with the PAM2 motif on Pan3 [ xref , xref , xref , xref , xref ]."
37398227
sparser
"Pan3 binds to the region of Pan2 that links its N‐terminalWD40 domain to the C‐terminal part that contains the exonuclease, with a 2:1 stoichiometry."
24872509
sparser
"Both Pan2-Pan3 and Ccr4-Not act specifically on poly(A) sequences."
34594027
sparser
"The crystal structure of the Pan2 linker region bound to a Pan3 homodimer shows how the unusual structural asymmetry of the Pan3 dimer is used to form an extensive high‐affinity interaction."
24872509
sparser
"Instead, this behavior is determined primarily by the interaction of Pan2–Pan3 with mRNA itself."
24872509
sparser
"To assess whether the zinc finger is the only component in the Pan2–Pan3 complex that binds directly to RNA, we deleted it from sc Pan3 and investigated the ability of the truncated sc Pan2–Pan3 complex to bind RNA."
24872509
sparser
"The experiments described above highlight the importance of association of Pan2 and Pan3 into a complex for their function in mRNA deadenylation, so we characterized how these two proteins interact at the molecular level in greater detail."
24872509
sparser
"These data are consistent with formation of a Pan2–Pan3 1:2 heterotrimer in solution."
24872509
sparser
"Interestingly, binding of ct Pan2 to ct Pan3 is mediated mainly by interactions between main chain atoms, not side chains."
24872509
sparser
"Because the ∆343–406 mutant retained significant activity compared to isolated ct Pan2, there may be additional sites of Pan2–Pan3 interaction, either within the PID (such as residues 316–342, Fig  xref A and S7D) or outside the PID."
24872509
sparser
"The Pan3 homodimer binds a single Pan2 chain, and the crystal structure of ct Pan3 bound to the interacting linker region of ct Pan2 (residues 355–406) shows an extensive interface between the two subunits consistent with the integral role of Pan3 in the overall function of the complex."
24872509
sparser
"Deadenylation is catalyzed by two major cytoplasmic deadenylase complexes, Pan2–Pan3, which initiates this process, and Ccr4-Not, acting at a later stage, finishing deadenylation prior to mRNA body decay ( xref ; xref )."
32820035
sparser
"NanoESI mass spectrometry, isothermal calorimetry, and a crystal structure of the interacting regions of ct Pan2 and ct Pan3 show that only one Pan2 molecule binds to a Pan3 dimer to form a heterotrimeric complex."
24872509
sparser
"Consistent with additional Pan2–Pan3 interactions, Pan2 ∆343–406 retained deadenylation activity (Fig  xref )."
24872509
sparser
"Structural features of poly(A) tail recognition by the Pan2–Pan3 deadenylase have been described, and the role of PABPs, together with poly(A), in forming a specific binding scaffold for the Pan2–Pan3 heterotrimer has been revealed ( xref )."
32820035
reach
"Mammalian cells contain three major poly (A)-specific 3 ' exoribonuclease activities : the CCR4-NOT (negative on TATA) and CAF1 complex, the PAN2 and PAN3 complex and PARN [poly (A)-specific ribonuclease]."
22817748
sparser
"In agreement with this, knockdown of Ccr4-Not components in mammalian cells results in an overall increase in mRNA half-lives but knockdown of Pan2-Pan3 does not have a major effect xref ."
34594027
reach
"Intriguingly, given its poly (A)-protective effect, PABP1 interacts directly with PARN and the PAN3 subunit of the PAN2 and PAN3 complex and indirectly with the CCR4, NOT, and CAF1 complex via TOB (transducer of ErbB2) 1 (or TOB2) [XREF_BIBR]."
22817748
reach
"Somewhat counterintuitively, given its poly (A)-protective effect, PABP1 also appears to enhance PAN2 and PAN3 complex activity and, via TOB mediated recruitment, CCR4-CAF1 deadenylase activity [XREF_BIBR, XREF_BIBR] (XREF_FIG, panel 1)."
22817748
reach
"The PAN2 and PAN3 complex hydrolyzes poly (A) in a distributive manner, while the CCR4 and NOT complex hydrolyzes poly (A) in a processive manner and is responsible for rapid deadenylation [13]."
25038453
sparser
"In yeast, canonical mRNA degradation typically occurs following shortening of the poly[A] tail (also referred to as deadenylation) by the Pan2-Pan3 and Pop2-Ccr4-Not complexes, followed by decay in either the 5’ to 3’ or the or the 3’ to 5’ direction ( xref ; xref )."
30560575
reach
"In Drosophila, there are two distinct deadenylase complexes : the CCR4 and NOT complex and the Pan2 and Pan3 complex 27."
30279526
reach
"The active PAN2 and PAN3 complex functions in both general and miRNA mediated mRNA deadenylation."
26589967
reach
"First, PAN2 (the catalytic subunit of the PAN2 and PAN3 complex) mediates the initial rapid deadenylation; then, two subunits of the CCR4 and NOT complex, CCR4 (CNOT6/6L) and Caf1 (CNOT7/8), are most likely responsible for shortening the polyA tail [XREF_BIBR, XREF_BIBR]."
24468964
reach
"The interaction of the PAN2 and PAN3 complex with PABP likely facilitates deadenylation."
24468964
sparser
"Deadenylases may act in multi-subunit complexes, such as the carbon catabolite repressor protein 4 (CCR4)-negative on TATA (NOT) complex (CCR4–NOT or CNOT) [ xref ], in heterocomplexes, including the Pan2–Pan3 complex consisting of a 1:2 stoichiometry [ xref , xref ], and oligomeric, such as the poly(A)-specific ribonuclease (PARN) [ xref , xref ]."
35630580
reach
"Second, direct biochemical interactions link miRNAs to Argonaute, Argonaute to TNRC6, and TNRC6 to the deadenylase complexes (the PAN2 and PAN3 complex and the CCR4 and NOT complex) that shorten the poly (A) tail, thereby showing how the mRNA degradation machinery can be actively recruited independent of either the act or the consequence of translational repression."
25263593
sparser
"Recent insights from biochemical reconstitution and structural biology have brought to light the dichotomous role of PABPC in mRNA life, the organizational principles of yeast Pan2-Pan3 on poly(A) RNP, and the important role that non-enzymatic components play in the CCR4-NOT complex (see below)."
36232288
sparser
"The Architecture and Recognition Mechanism of Poly(A) RNP by Pan2-Pan3 Complex."
36232288
sparser
"The recent cryo-EM reconstruction of the yeast Pan2-Pan3 in complex with a poly(A) RNP composed of 90 adenosines and three Pab1 has illuminated the molecular mechanism for why Pan2-Pan3 preferentially acts on a longer poly(A) RNP and how Pab1 stimulates this process ( xref ) [ xref ]."
36232288
sparser
"The Pab1-90A RNP binds to one side of the Pan2-Pan3 complex ( xref B,C)."
36232288
sparser
"The architecture of the poly(A) RNP in this structure interestingly presents repeated arches, which are shaped by RRM3, the Pab1-Pab1 oligomerization interface, and the interacting position with Pan2-Pan3 ( xref C–E)."
36232288
sparser
"Deadenylation by the major deadenylases Pan2-Pan3 and Ccr4-Not initiate poly(A) tail shortening and removal of the stabilizing Poly(A) Binding Protein (Pabpc) from the 3’ end of transcripts ( xref ; xref ; xref ; xref )."
31656086
sparser
"In summary, Pab1 stimulates deadenylation by providing the main structural features for the Pan2-Pan3 complex recognition, which is critical for its length specificity."
36232288
reach
"27 In addition, Pbp1 negatively regulates the activity of the poly (A)-nuclease (PAN) by interacting with the subunit Pan2 of the PAN complex Pan2 and Pan3."
15663938
reach
"This is in contrast to the PAN2 and PAN3 complex, which interacts directly with PABP via a PAM2 motif in PAN3."
24904637
sparser
"Although structural analyses have unveiled why yeast Pan2-Pan3 works on longer poly(A) tails [ xref ], the structural details of the CCR4-NOT complex and how PABPC affects CCR4-NOT at the molecular level remain to be determined."
36232288
reach
"The PAN2 and PAN3 complex is involved in an early phase of deadenylation and degrades the mRNA poly (A) tail in a distributive manner to ~ 50-110 nucleotides, depending on the organism and the specific mRNA."
22977175
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"Decay is generally initiated by deadenylation that is mediated by multiple deadenylases such as the Pan2 and Pan3 complex and the Ccr4 and Not complex."
25480299
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"One study has described a series of coupled events starting with the recruitment of the translation termination factors eRF1 and eRF3, recruitment of the minor deadenylation complex Pan2 and Pan3, and finally recruitment of Ccr4-Not by the BTG and TOB family of proteins via their interaction with PABP.88 BTG and TOB proteins are absent in budding and fission yeast and they are not constitutively expressed in mammalian cells (for reviews see Ref 89)."
26821858
sparser
"However, it's worth noting that translation termination complexes, including eRF1-eRF3, Pan2-Pan3, and Caf1-Ccr4, can competitively interact with the polyadenylate-binding protein PABPC1 to mediate mRNA deadenylation [ xref ]."
39039334
sparser
"mRNAs are first trimmed and/or deadenylated at the 3’ end by the Pan2-Pan3 and CCR4-NOT complexes, and then undergo decapping, removal of the 5’ 7-methylguanosine cap by Dcp2, before being degraded by Xrn1."
37808861
sparser
"Although Ccr4-Not has roles in many aspects of regulating gene expression (e.g., chromatin remodeling, transcription, mRNA export, and RNA interference), its most defined and best understood role is in mRNA degradation, serving as the major cytoplasmic deadenylase other than Pan2-Pan3 ( xref , xref )."
32299921
sparser
"For deadenylation, mRNA deadenylase complexes (e.g., Caf1–Ccr4 and Pan2–Pan3) cleave the 3′ poly A tail, leading to mRNA decay [ xref ]."
36839942
sparser
"Specifically, we discuss the roles of poly(A) tails in translation and mRNA stability, and how poly(A) tails are removed by exonucleases (deadenylases) including Ccr4-Not and Pan2-Pan3."
34594027
sparser
"Here, we review the roles of poly(A) tails in the cytoplasm – specifically in translation and mRNA stability – and the mechanisms of poly(A) tail removal by the Ccr4-Not and Pan2-Pan3 deadenylation complexes."
34594027
sparser
"Two protein complexes account for the major cytoplasmic deadenylation activities in eukaryotes: Pan2-Pan3 and Ccr4-Not ( xref )."
34594027
sparser
"Although Pan2 and Pan3 can form a complex in the cytoplasm, the finding that HA-Pan3 can be detected in P-bodies when it is overexpressed alone ( xref ) suggests that Pan3 can associate with P-bodies without a coordinated expression of Pan2."
18625844
sparser
"The genes encoding Pan2 and Pan3 are not essential in yeast: deletion of either gene results in longer poly(A) tails at steady state but does not eliminate deadenylation because Pan2-Pan3 is partially redundant with Ccr4-Not xref , xref ."
34594027
sparser
"Pan2-Pan3 is recruited to poly(A) RNA through at least three interactions: a Pan3 N-terminal zinc finger specifically binds adenosines xref , a PAM2 motif in Pan3 binds PABPC xref , and additional regions of the complex interact with the PABPC:poly(A) RNP xref ."
34594027
sparser
"Thus, by recruiting Pan2-Pan3 to poly(A) RNA, Pab1 stimulates deadenylation."
34594027
sparser
"Pan2-Pan3 does not appear to substantially affect mRNA half-life and may be more important under specific cellular circumstances."
34594027
sparser
"The exonuclease active site of Pan2 additionally selects for poly(A) RNA because it recognizes an intrinsic, single-stranded helical conformation of RNA that is uniquely formed by poly(A) ( xref ) xref Pan2-Pan3 can be recruited to specific transcripts via an interaction with the GW182 protein within the miRNA-induced silencing complex (miRISC) xref , xref , but it remains unclear how or if Pan2-Pan3 is specifically recruited to other transcripts."
34594027
sparser
"Pan2-Pan3 was first identified through fractionation of yeast extracts and it contains a DEDD/RNaseD-type exonuclease in its Pan2 subunit xref – xref ."
34594027
sparser
"The activity of the Ccr4-Not complex may be more processive than Pan2-Pan3 in many cases, and this may account for its more rapid deadenylation."
34594027
sparser
"These results are consistent with previous findings that Pan3 is a genuine PABP binding protein ( xref ) and that Pan2 and Pan3 can form complexes in vivo ( xref )."
18625844
sparser
"One hypothesis is that the major deadenylation complexes act in a biphasic (or sequential) model of deadenylation where Pan2-Pan3 removes the distal part of the poly(A) tail and Ccr4-Not removes adenosines more proximal to the 3′-untranslated region (UTR) ( xref )."
34594027
sparser
"The poly(A)-Pab1 RNP winds across the surface of Pan2-Pan3 in a zigzag configuration ( xref )."
34594027
sparser
"It will be interesting to determine how the mammalian Pan2-Pan3 achieves a similar function on longer poly(A) tails."
34594027
sparser
"It remains unclear whether Pan2-Pan3 activity is regulated (e.g. by translation), whether Pan2-Pan3 is targeted to specific transcripts by multiple different RNA adapter proteins, or whether it acts as a general factor to ‘trim’ long poly(A) tails."
34594027
sparser
"The microRNA-induced silencing complex (miRISC) also mediates targeted deadenylation as its GW182 subunit interacts directly with the Pan2-Pan3 and Ccr4-Not complexes xref ."
34594027
sparser
"This model therefore suggests that as the poly(A) tail is shortened, its affinity for Pan2-Pan3 progressively decreases."
34594027
sparser
"Cytosines and uracils are removed by Pan2-Pan3 slightly less efficiently than guanosine but Ccr4-Not is more selective xref ."
34594027
sparser
"Although Ccr4-Not activity removes the final part of the poly(A) tail, and is often thought of as being ‘faster’ than Pan2-Pan3, it is clear that it does not act equally on all short poly(A) tails because stable, highly-translated transcripts are more resistant to deadenylation."
34594027
reach
"The Pan2 and Pan3 complex has been identified in HeLa cells, where its activity is also stimulated by polyadenylate binding protein (PABP) [XREF_BIBR]."
18096048
sparser
"Recently, structures of Pan2-Pan3 complexes from Neurospora crassa [23] and S. cerevisiae [24] were published, indicating its asymmetrical architecture with 1:2 Pan2:Pan3 stoichiometry."
27713097
reach
"The 3 ' poly (A) tail and PABP complex stimulates poly (A) shortening by the Pan2 and Pan3 complex but inhibits the activity of the Ccr4 and Caf1 complex."
23224971
sparser
"For regular mRNA degradation the decay process is initiated with the gradual shortening of the 3′ poly(A)-tail by the Ccr4:Not and Pan2:Pan3 complexes ( xref xref – xref )."
32723815
sparser
"It is now established, that cytoplasmic deadenylase activity comes predominantly from Ccr4-Not and Pan2-Pan3 complexes (reviewed in [15] ) ( Fig. 1 A)."
27713097
sparser
"As mentioned earlier, a second deadenylation activity in eukaryotes is provided by the Pan2-Pan3 complex ( Fig. 1 A), which does not degrade poly(A) tails completely in vitro or in vivo [15] , so it i[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
27713097
sparser
"This mutant panel affects proteins for key pathways of RNA processing and degradation: Rrp6 , a 3′-5′ exonuclease of the nuclear RNA exosome ( xref ; xref ); Dis3 , a 3′-5′ exo/endonuclease of the core RNA exosome ( xref ); Ago1 (Argonaute), Dcr1 (RNase III-like Dicer), and Rdp1 (RNA-dependent RNA polymerase) of the RNAi pathway ( xref ); Exo2, a cytoplasmic 5′ exonuclease (ortholog of XRN1) ( xref ); Ski7, a cytoplasmic cofactor which links the Ski complex to the exosome ( xref ); Cid14, a poly(A) polymerase of the TRAMP complex which is a cofactor of the nuclear RNA exosome ( xref ); Pab2, a poly(A)-binding protein targeting RNAs to the nuclear exosome (PABPN1 ortholog) ( xref ); Pan2, a deadenylase of the Pan2–Pan3 complex ( xref ); and Upf1, an ATP-dependent RNA helicase of the NMD pathway ( xref )."
29914874
sparser
"Additionally, yeast and human Pan2 interacts with Pan3, and human PAN3 mediates PAN2 recruitment to mRNA through PABPs [15] ."
27713097
reach
"Recent studies have identified the Pan2 and Pan3 complex and the Ccr4 and Caf1 transcription factors as part of a large complex that possesses deadenylating activity (Boeck et al., 1996; Brown and Sac[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
11674994
sparser
"Since the physiological consequences of knockout or knockdown of Ccr4-Not complex subunits are far stronger than in the case of Pan2-Pan3 dimer, the former seems to be the only deadenylase essential f[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
27713097
sparser
"Interestingly, both the constituents of deadenylase complexes (Ccr4-Not and Pan2-Pan3) and factors implicated in the pathways mentioned above were found in P-bodies [15] ."
27713097
reach
"The Pan2 and Pan3 complex is thought to play a role in either initiating or subsequently trimming the poly-A tails in support of Ccr4, Caf1, and Not complex activity."
22126454
sparser
"The crystal structure of an active ~200-kDa core complex reveals that Pan2 and Pan3 interact with an unusual 1:2 stoichiometry imparted by the asymmetric nature of the Pan3 homodimer."
24880344
reach
"Of the other parasitic protists examined to date for deadenylation machinery, Trypanosoma brucei has been shown to contain both the Ccr4 -Not complex and the Pan2 and Pan3 complex [XREF_BIBR, XREF_BIBR], while Plasmodium falciparum contained a majority of the required components of the Ccr4 and Not complex but was also missing the Pan2 and Pan3 complex [XREF_BIBR]."
22126454
reach
"ARE mediated mRNA decay requires the involvement of many enzymes required for the deadenylation (Pan2 and Pan3 complex), decapping (e.g., Dcp1a, Hedls) and RNA degradation (e.g., XRN1) of the target mRNA."
26343742
reach
"In metazoans and yeast, the Ccr4, Caf1, and Not complex has the predominant deadenylase activity, while the Pan2 and Pan3 complex may trim poly (A) tails to the correct size, or initiate deadenylation."
19596809
reach
"In yeast and animals, the roles of the PAN2 and PAN3 complex may be mainly in quality control -- trimming poly (A) tails in the nucleus and cytoplasm."
19596809
reach
"Only the PAN2 subunit of the PAN2 and PAN3 complex is endowed with nuclease activity; PAN3 is an essential auxiliary factor."
19828319
sparser
"Biochemical and structural studies of yeast factors indicate that Pan2-Pan3 can efficiently trim long PATs with serially bound PABP in part because of a unique architecture of PABP-PABP interactions on poly(A), whereas Pan2-Pan3 is inefficient on short poly(A)-PABP mRNPs ( xref )."
32744499
sparser
"The relative contribution of the deadenylases, especially Ccr4-Not and Pan2-Pan3 complexes to overall deadenylation activity is not entirely clear, but it is established that it varies depending on th[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
27713097
sparser
"Notwithstanding, some experiments suggest that in certain cases Ccr4-Not and Pan2-Pan3 may have partially overlapping functions."
27713097