IndraLab

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"Deadenylation is triggered by deadenylases, which include the CCR4 and NOT complex, the PAN2 and PAN3 complex and PARN in mammals."

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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)."

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"Moreover, interactions between eIF4G and the poly [A] binding protein Pab1 are capable of mediating interactions between the 5 ' and 3 ' ends of mRNA [XREF_BIBR], whereby Pab1 stimulates both translation initiation [XREF_BIBR, XREF_BIBR] and deadenylation by the Pan2 and Pan3 complex [XREF_BIBR]."

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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]"

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"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."

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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."

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"Two protein complexes account for the major cytoplasmic deadenylation activities in eukaryotes: Pan2-Pan3 and Ccr4-Not ( xref )."

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"Although Pan3 and Caf1 associate with Pan2 and Ccr4 poly (A) nucleases, respectively, their in vivo roles in mammalian mRNA turnover remain unclear."

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"POP2, like PARN and PAN2, the catalytic subunit of the Pan2 and Pan3 complex, is a member of the DEDD nuclease family."

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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]"

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"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."

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"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."

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."

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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."

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"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]"

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"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]."

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"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."

sparser
"In contrast, the presence of guanosines within the poly(A) tail inhibits both Pan2Pan3 and Ccr4–Not ( xref )."

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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."

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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."

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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."

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"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]."

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"Structural basis of Chaetomium thermophilum Pan2 and Pan3 complex formation."

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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]"

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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 and Pan3 complex [XREF_BIBR]."

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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."

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"Pbp1 regulates the Pan2-Pan3 deadenylase complex, thereby modulating the mRNA stability and translation efficiency."

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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."

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"The poly (A) tail degrading enzyme Pan2-Pan3 complex has been reported to be inhibited by Pbp1 [ xref ]."

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"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 )."

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"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 )."

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"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."

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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."

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"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."

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"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."

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"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."

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"Dissection of the specific roles of the Pan2 and Pan3 complex and PARN is currently being pursued."

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"Only the PAN2 subunit of the PAN2 and PAN3 complex is endowed with nuclease activity; PAN3 is an essential auxiliary factor."

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"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."

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"Within the other major deadenylase complex, Pan2Pan3, several domains and motifs contribute to poly(A) specificity."

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"The Pan2 and Pan3 complex has been identified in HeLa cells, where its activity is also stimulated by polyadenylate binding protein (PABP) [XREF_BIBR]."

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"The PAN2 and PAN3 complex is a heteromultimer in which PAN2 is the catalytically active deadenylase subunit XREF_BIBR."

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"Our results suggest that the Pan2-Pan3 complex, together with the Ccr4-Not complex, has important roles in the growth on non-fermentable carbon sources."

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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."

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"PAN3 interacts with the catalytic subunit PAN2 (Mangus et al., 2004)."

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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]."

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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]."

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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 and Pan3 complex to the poly (A) tail."

sparser
"Pan2-Pan3 does not appear to substantially affect mRNA half-life and may be more important under specific cellular circumstances."

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"Once a single Pab1 is left, the poly(A) RNP is inefficiently bound and deadenylated by Pan2-Pan3."

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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]"

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 )."

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"The poly(A)-Pab1 RNP winds across the surface of Pan2-Pan3 in a zigzag configuration ( xref )."

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"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."

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"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."

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"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."

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"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 )."

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"Our results suggest that the Pan2 and Pan3 complex, together with the Ccr4 and Not complex, has important roles in the growth on non fermentable carbon sources."

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"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."

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"To establish the stoichiometry of the Pan2 and Pan3 complex, we used non covalent nanoelectrospray ionization mass spectrometry (nanoESI-MS)."

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"Both Pan2-Pan3 and Ccr4-Not act specifically on poly(A) sequences."

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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."

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"Pan2Pan3 is composed of one Pan2 and two Pan3 molecules ( xref ; xref , xref ; xref )."

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"The lack of inhibitory effect by uracils on Pan2Pan3 and Ccr4–Not suggests that the oligo(U) tail alone does not impede deadenylation ( xref )."

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"Pan2-Pan3 complex, together with Ccr4-Not complex, has a role in the cell growth on non-fermentable carbon sources."

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"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."

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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)."

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"Deadenylation in yeast is carried out by the Pan2 and Pan3 complex as well as the by Ccr4, Pop2, and Not complex."

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"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."

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"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)."

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"The active PAN2 and PAN3 complex functions in both general and miRNA mediated mRNA deadenylation."

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"To assess whether the zinc finger is the only component in the Pan2Pan3 complex that binds directly to RNA, we deleted it from sc Pan3 and investigated the ability of the truncated sc Pan2Pan3 complex to bind RNA."

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"Since Pan2-Pan3 recognizes the Pab1 oligomerization interface, it preferentially acts on poly(A) RNA that is long enough to accommodate multiple Pab1 molecules."

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"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."

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"Seven deadenylases have been identified in C. elegans via homology, belonging to the Ccr4-Not complex, the Pan2-Pan3 complex, or orthologs of individual deadenylase family members PARN, Angel, and 2′ phosphodiesterase ( xref )."

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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)."

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"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."

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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."

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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]."

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."

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"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 ."

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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."

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"COX10 , COX11 , and AIM33 mRNA are not regulated by Pbp1 via the Pan2-Pan3 complex and the Ccr4-Not complex."

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"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."

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"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."

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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."

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"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."

sparser
"In C. elegans , loss of the Ccr4-Not components caused significant lengthening of poly(A) tails, while loss of Pan2-Pan3 complex components or PARN genes did not cause longer poly(A) tails but only reduced the abundance of short poly(A) tails ( xref )."

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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."

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"Pan2-Pan3 was first identified through fractionation of yeast extracts and it contains a DEDD/RNaseD-type exonuclease in its Pan2 subunit xref – xref ."

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"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 )."

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"These data indicated that a Pan3 dimer might bind two copies of Pan2 with an overall stoichiometry of 2:2."

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"We show by coimmunoprecipitation and directed two-hybrid studies that the Pan2 and Pan3 proteins physically interact."

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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."

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"In our in vitro deadenylation assay, the Pan2 and Pan3 complex alone completely deadenylates RNA (Fig XREF_FIG C)."

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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."

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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]"

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 )."

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"The mechanism of Pan2 and Pan3 complex formation and substrate binding remain elusive."

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."

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 ."

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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 Pan2Pan3 complex to the poly(A) tail ( xref )."

sparser
"Interestingly, binding of ct Pan2 to ct Pan3 is mediated mainly by interactions between main chain atoms, not side chains."

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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]."

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"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."

sparser
"Binding of the Pan2Pan3 complex requires the interaction of the N- and C-term regions surrounding the RRM [ xref , xref ]."

sparser
"Because the ∆343–406 mutant retained significant activity compared to isolated ct Pan2, there may be additional sites of Pan2Pan3 interaction, either within the PID (such as residues 316–342, Fig  xref A and S7D) or outside the PID."

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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."

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"Cytosines and uracils are removed by Pan2-Pan3 slightly less efficiently than guanosine but Ccr4-Not is more selective xref ."

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"Of particular interest was pan3Delta, which encodes a subunit of the Pan2 and Pan3 complex."

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"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 ."

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"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."

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"The fission yeast genome encodes two additional presumptive deadenylases, namely the Pan2 and Pan3 complex and PARN."

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"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."

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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 Pan2Pan3 complex xref ."

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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."

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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."

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"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."

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"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."

sparser
"In eukaryotes, deadenylation is primarily performed by two highly conserved multiprotein complexes, Pan2Pan3 and Ccr4–Not, that shorten the poly(A) tail in a 3’–5’ direction."

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"Eukaryotic mRNA deadenylation is generally considered as a two-step process in which the PAN2 and PAN3 complex initiates the poly (A) tail degradation while, in the second step, the CCR4 and NOT complex completes deadenylation, leading to decapping and degradation of the mRNA body."

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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]"

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."

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"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 )."

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."

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"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 )."

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"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."

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"These data are consistent with formation of a Pan2Pan3 1:2 heterotrimer in solution."

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"This deadenylation is carried out by the Pan2 and Pan3 complex as well as by the Ccr4 and Not complex."

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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."

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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)."

sparser
"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."

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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."

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."

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"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."

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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."

sparser
"This model therefore suggests that as the poly(A) tail is shortened, its affinity for Pan2-Pan3 progressively decreases."

sparser
"However, co-immunoprecipitation analysis indicated that PAN3 was physically associated with USP52 as reported xref , xref , but not with ASF1A (Fig.  xref )."

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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."

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"In Drosophila, there are two distinct deadenylase complexes : the CCR4 and NOT complex and the Pan2 and Pan3 complex 27."

sparser
"To determine the nucleotide specificities of the DEDD exonucleases Caf1 and Pan2, we used in vitro biochemical assays with recombinant Pan2Pan3 or with Ccr4–Not containing a catalytic mutant of Ccr4 (such that Caf1 was the only active nuclease) ( xref )."

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."

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"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]."

sparser
"There are two major deadenylase complexes, Ccr4-Not and Pan2-Pan3, which shorten the 3' poly(A) tail of mRNA and are conserved from yeast to human."

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."

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"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]."

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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]"

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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]."

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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."

sparser
"Consistent with additional Pan2Pan3 interactions, Pan2 ∆343–406 retained deadenylation activity (Fig  xref )."

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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]."

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"Pan2 and Pan3 complex, together with Ccr4 and Not complex, has a role in the cell growth on non fermentable carbon sources."

reach
"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)."

reach
"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)."

reach
"Because Pan3 is a dimer, there are two zinc fingers and two PAM2 motifs in each Pan2 and Pan3 complex."

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."

No evidence text available

sparser
"Instead, this behavior is determined primarily by the interaction of Pan2Pan3 with mRNA itself."

reach
"In contrast, Pan2 and Pan3 complex containing a catalytic mutation in Pan2 (E912A) did not have nuclease activity (XREF_SUPPLEMENTARY)."

reach
"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."

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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."

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."

sparser
"Thus, by recruiting Pan2-Pan3 to poly(A) RNA, Pab1 stimulates deadenylation."

reach
"Structural basis for Pan3 binding to Pan2 and its function in mRNA recruitment and deadenylation."

sparser
"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 ."

sparser
"Two distinct catalytic subunits, Caf1/Pop2 and Ccr4, are associated with the Ccr4-Not complex, whereas the Pan2 enzymatic subunit forms a stable complex with Pan3."

sparser
"As the first step of mRNA decay, deadenylation is first carried out by the Pan2Pan3 complex and further digested by the Ccr4-Not complex (for review, see xref )."

sparser
"It will be interesting to determine how the mammalian Pan2-Pan3 achieves a similar function on longer poly(A) tails."

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]."

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]"

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"The PAN2 and PAN3 complex functions in general and microRNA mediated mRNA deadenylation."

No evidence text available

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"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]."

reach
"PolyA binding protein stimulates the reaction but is not required, suggesting that this function is intrinsic to the Pan2 and Pan3 complex."

sparser
"Deadenylation is performed by the Pan2Pan3 and Ccr4–Not complexes that contain highly conserved exonuclease enzymes Pan2, and Ccr4 and Caf1, respectively."

sparser
"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 ]."

reach
"The interaction of the PAN2 and PAN3 complex with PABP likely facilitates deadenylation."

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."

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 ."

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"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]."

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 ."

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."

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."

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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."

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)."

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]."

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 )."

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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]"

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"In humans, TNRC6C also independently interacts with the PAN2 and PAN3 complex and contributes to gene silencing by miRNA."

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"Furthermore, we found that Pbp1 together with the Pan2 and Pan3 complex regulates LRG1 poly (A) tail in vivo."

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"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]."

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."

reach
"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."

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"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]."

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"This is in contrast to the PAN2 and PAN3 complex, which interacts directly with PABP via a PAM2 motif in PAN3."

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"PAN3, in turn, binds to PABPC1 and PAN2 and may act as a bridging factor."

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"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]."

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"Together, our data reveal the structural basis for the interaction of PAN3 with PAN2 and the recruitment of the PAN2 and PAN3 complex to miRNA targets by TNRC6 proteins."

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"The Pan2 and Pan3 complex is widely conserved among eukaryotes."

reach
"Thus, the purified Pan2 and Pan3 complex is an active deadenylase in vitro and appears to have an intrinsic ability to bind polyA RNA."

No evidence text available