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PAN2 binds NLRP6. 93 / 93
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"Two major complexes are involved in mRNA deadenylation: the Ccr4/Pop2/Not complex and Pan2/Pan3 complex [16] ."
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"In addition, YTHDF3 coimmunoprecipitated with PAN3 ( Figure 2 C), demonstrating that YTHDF3 recruits the PAN2-PAN3 complex to digest poly(A) via an RNA decay pathway different from that used by YTHDF2[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Overexpression of only YTHDF2 could rescue the phenotype ( Figures 2 D, 2E, and S2 H), suggesting that the function of YTHDF3 depends on the PAN2-PAN3 complex."
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"Although the PAN2-PAN3 complex can associate with the CCR4-NOT complex ( Zheng et al., 2008 ), the molecular details and mechanism for the consecutive action of these complexes are unclear.The PAN2-PA[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Deadenylation is therefore the major step in controlling mRNA decay and as such is highly regulated.Three enzymes with deadenylase activity are present in most species, the CCR4-NOT complex, the PAN2-[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"In this review, we will focus on the main cytoplasmic deadenylases: the Pan2–Pan3 complex and the multisubunit Ccr4–Not complex."
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"In plants, the PAN2–PAN3 complex has not yet been identified."
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"First, the catalytic subunit of the PAN2–PAN3 complex PAN2 mediates the initial rapid deadenylation, followed by two subunits of the CCR4–NOT complex, CCR4 and CAF1, most likely shortening the poly(A)[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"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] ."
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"These results demonstrate that the Caf1–Ccr4–Tob complex, but not the Pan2–Pan3 complex, is responsible for c-myc mRNA deadenylation."
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"Also, Ago2 interacts with GW182 which in turn associates with CCR4-NOT complex, PAN2/PAN3 complex as well as PABP leading to mRNA degradation (Wilczynska and Bushell, 2015)."
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"Poly(A) tails are first trimmed to approximately 50–110 nt by the distributive activity of the PAN2-PAN3 complex, after which the shortened mRNA tails are rapidly degraded by the CCR4-NOT complex ( Tu[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Accordingly, PAN2 is inactive in the absence of PAN3, and the activity of the PAN2-PAN3 complex is stimulated by PABP ( Boeck et al., 1996; Brown et al., 1996; Lowell et al., 1992; Uchida et al., 2004[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"In addition to the interaction between PAN3 and PABP, which plays a role in general mRNA deadenylation, other examples of RNA-associated proteins that recruit the PAN2-PAN3 complex to specific mRNA ta[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Furthermore, proteins of the GW182 family (known as TNRC6A–C in humans), which are required for miRNA-mediated gene silencing in animals, interact directly with PAN3, thereby recruiting the PAN2-PAN3 [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"However, no structural information has been obtained for the PAN2-PAN3 complex."
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"Thus, the PK+C fragment mediates PAN3 homodimerization, and this function is conserved from yeast to humans.Given the importance of the PK and C-term domains in the assembly of the PAN2-PAN3 complex, [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"PAN3 dimerization and binding to PAN2 were not affected by the M7 mutation ( Figures 4 D and 4E, lanes 11; and Figures S4 C and S4D), indicating that the M7 mutant is properly folded."
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"Because the M8 deletion does not affect PAN2 binding ( Figure S4 F), these results suggest that mRNA degradation by the PAN2-PAN3 complex requires conformational rearrangements or the interaction with[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Our study provides a detailed molecular model for the assembly of the PAN2-PAN3 complex that significantly improves our understanding of PAN2-PAN3-mediated mRNA degradation.Our data demonstrate that P[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"It is possible that other protein partners similarly use this pocket to recruit the PAN2-PAN3 complex to their targets or to regulate its activity.PAN2 recruitment to mRNA targets is dependent on its [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"In conclusion, the structural and functional insights into PAN3-PAN2 and PAN3-TNRC6 interactions, the identification of a conserved surface in the PK domain required for mRNA degradation, and the find[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"In the standard view, poly(A) tails on human mRNAs are initially trimmed by the Pan2-Pan3 complex."
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"One possibility is that different subunits of the complex serve to recruit CAF1 to its mRNA substrates for long enough to dislodge PABP.PAN2 is an additional deadenylase, associated with a second prot[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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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 ]."
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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.To further investigate t[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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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.Strains used in this study are described in[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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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."
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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.The gluconeogenesis gen[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"PAN3, a regulatory subunit of the PAN2-PAN3 complex, was involved in the metabolism of messenger RNA (41)."
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"A newly transcribed transcript is known to receive a poly(A) tail of ∼230 nt, and they are gradually shortened by deadenylases PARN, the PAN2-PAN3 complex, and the CCR4-NOT complex ( Garneau et al., 2[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"The Pab1-90A RNP binds to one side of the Pan2-Pan3 complex (Figure 6B,C)."
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"In summary, Pab1 stimulates deadenylation by providing the main structural features for the Pan2-Pan3 complex recognition, which is critical for its length specificity."
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"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 (Fig. 1G; Supplemental Fig. S1C)."
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"In addition to the CCR4-NOT complex, PAN3, the subunit of the PAN2-PAN3 complex, was also present in this pathway (Figure 2B)."
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"Generally, mRNA decay starts with deadenylation by a deadenylase complex, such as the CCR4-NOT complex or the PAN2/PAN3 complex."
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"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]"
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"The poly(A)-binding protein (PABP) that coats the poly(A) tail stimulates the PAN2-PAN3 complex, leading to more efficient activity on longer tails that are coated by multiple PABP molecules [3,4]."
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"The PAN2-PAN3 complex can be recruited to microRNA targets [8] and is generally stimulated by the presence of PABP on the poly(A) tail [4]."
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"Further, it will be imperative to look beyond CCR4-NOT itself and assess its role in conjunction with other factors in mRNA decay, such as the PAN2-PAN3 complex and the downstream decay factors."
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"The CCR4-NOT complex is the main effector of deadenylation, whilst the PAN2-PAN3 complex has a fairly limited role [73]."
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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 (Boeck et al., 1996; Brown et al., 1996; Tucker et al., 2001; Yamashita et al., 2005; Wahle and Winkler, 2013)."
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"Deadenylation: the Pan2-Pan3 complex."
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"The Pan2-Pan3 complex is highly conserved (Uchida et al., 2004; Wahle and Winkler, 2013) with an atypical architecture in which an asymmetric Pan3 homodimer is bound by a single Pan2 subunit (Pan2:Pan3 = 1:2) (Jonas et al., 2014; Schafer et al., 2014; Wolf et al., 2014)."
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"Pan3 forms an asymmetric homodimer when assembled into the yeast Pan2-Pan3 complex (Christie et al., 2013; Jonas et al., 2014; Schafer et al., 2014; Wolf et al., 2014)."
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"Moreover, the ability for nucleotide binding seems required for the ribonuclease activity of the Pan2-Pan3 complex (Christie et al., 2013)."
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"Recently, the PAN2/PAN3 complex has been found to be responsible for deadenylation process, which removes the poly(A) tail from RNA; while another study reports that PAN3 rearrangement may be involved[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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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 (Wolf et al., 2014; Schafer et al., 2019)."
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"The TNRC6s, in turn, recruit downstream effectors—general translation inhibition and/or mRNA destabilization machinery such as the CCR4–NOT and PAN2–PAN3 complexes.There remain gaps in our understanding of miRNA-regulatory actions."
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"The Pan2-Pan3 complex recognises a RNP containing a 90-mer poly(A) bound to three PABPC molecules through two main interactions (Figure 2D)."
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"It is known that the host gene of circPAN3, PAN3 , is located at chromosome 13q12 and its protein product serves as a regulatory subunit of the PAN2/PAN3 complex [ 40 ]."
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"The miRNA- Argonaute family complex recruits the CCR4-NOT complex or the PAN2-PAN3 complex, leading to degradation of target mRNAs (64, 65)."
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"This mutant panel affects proteins for key pathways of RNA processing and degradation: Rrp6, a 3′-5′ exonuclease of the nuclear RNA exosome (Harigaya et al. 2006; Lemay et al. 2014); Dis3, a 3′-5′ exo/endonuclease of the core RNA exosome (Wang et al. 2008); Ago1 (Argonaute), Dcr1 (RNase III-like Dicer), and Rdp1 (RNA-dependent RNA polymerase) of the RNAi pathway (Volpe et al. 2002); Exo2, a cytoplasmic 5′ exonuclease (ortholog of XRN1) (Houseley and Tollervey 2009); Ski7, a cytoplasmic cofactor which links the Ski complex to the exosome (Lemay et al. 2010); Cid14, a poly(A) polymerase of the TRAMP complex which is a cofactor of the nuclear RNA exosome (Wang et al. 2008); Pab2, a poly(A)-binding protein targeting RNAs to the nuclear exosome (PABPN1 ortholog) (Lemieux et al. 2011); Pan2, a deadenylase of the Pan2–Pan3 complex (Wolf and Passmore 2014); and Upf1, an ATP-dependent RNA helicase of the NMD pathway (Rodríguez-Gabriel et al. 2006)."
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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)."
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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]"
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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."
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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 20, whereby Pab1 stimulates both translation initiation 21, 22 and deadenylation by the Pan2/Pan3 complex 23."
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"The major players in this regulation are poly(A)-specific ribonuclease (PARN), the CCR4–NOT complex, and the PAN2–PAN3 complex [25,26] ."
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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 23."
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"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]"
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"As the heart of RISC, Argonaute2 (Ago2) recruits TNRC6, PABPC, and deadenylase complexes, i.e., the PAN2-PAN3 complex or CCR4-NOT complex to destabilize or repress mRNA [15–17]."
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"Arguing against a strictly inhibitory role of PABPC with respect to deadenylation, the PAN2/PAN3 heterodimeric exonuclease is conserved in mammals and other higher eukaryotes, and this enzyme, like it[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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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]"
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"However, it has been proved that miRISC consists of many other components: GW182 proteins (a family of proteins rich in tryptophan and glycine repeats, specifically TNRC6A-C in humans), the CCR4-NOT complex (carbon catabolite repression—negative on TATA-less complex), the PAN2/PAN3 complex (two subunits of the poly(A)-specific ribonuclease PAN complex), DCP1 (decapping protein 1), DDX6 (RNA helicase), and GIGYF2 (GRB10 interacting GYF protein 2)."
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"Additionally, the PAN2/PAN3 complex contributes to miRNA-induced deadenylation."
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"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) [3], in heterocomplexes, including the Pan2–Pan3 complex consisting of a 1:2 stoichiometry [4,5], and oligomeric, such as the poly(A)-specific ribonuclease (PARN) [6,7]."
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"GW182 protein serves as a hub protein, and recruits several factors to the target mRNAs including poly(A)-binding protein (PABP) and two deadenylase complexes, CCR4–NOT and PAN2–PAN3 complexes ( Box 1[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"These results indicate that CCR4–NOT complex, rather than PAN2–PAN3 complex, is the major trigger of miRNA-mediated deadenylation and mRNA decay ( Figure 1 ) [20,22,24–26,47] ."
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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 )."
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"Indeed, eukaryotic mRNA decay typically begins with poly(A) tail shortening by exonucleases, including the poly(A)-specific ribonuclease (PARN), Pan2/Pan3 complex and CCR4–NOT complex ."
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"The second, more rapid phase of deadenylation is catalyzed by the CCR4-CAF1-NOT complex ( Stinton et al., 2004 ) which can rescue the cytoplasmic mRNA deadenylation even in the absence of the PAN2–PAN[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Most of these PAM2 motif-containing proteins are involved in mRNA translation and processing, including eukaryotic release factor 3 (eRF3), the deadenylase complex PAN2/PAN3 and TOB1/2 proteins regulating the CCR4-NOT deadenylase complex, and the GW182 protein family."
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"A biphasic model is proposed for deadenylation: in the initial phase, poly(A)-binding protein PABPC1 facilitates the loading of the PAN2–PAN3 complex to remove the distal part of poly(A) tail through the distributive exonuclease PAN2."
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"These findings imply a complicated and subtle interaction network comprising the PAN2–PAN3 complex, poly(A) RNPs (ribonucleoprotein complexes of poly(A)-binding proteins), and other factors which co-operatively promote deadenylation [12,40]."
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"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 (Yamashita et al., 2005)."
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"The poly(A) tail recruits PAN2–PAN3 through at least three interactions: between the PAN3 N-terminal zinc finger and adenosines in the poly(A) tail; between PAN3 and a PAM2 motif in PABP; and between additional regions of the PAN2–PAN3 complex and the PABPC–poly(A) RNP [12,52,118]."
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"In mammals, the decay of mRNA starts with PAN2–PAN3 complex formation, which mediates shortening of the poly(A) tail to ~110 nt [123]."
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"CCR4/CAF1/NOT acts sequentially with PAN2/PAN3 complexes to mediate 3′-5′ exonucleolytic degradation of poly(A) tails."
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"The mechanism by which miRNA takes effect is through inhibition of translation assembly: miRNA competes with eIF4E at the m7G cap site of the mRNA, while promoting deadenylation, decapping, and degradation of the mRNA through recruitment of the PAN2-PAN3 complex, the CCR-NOT complex, and exoribonuclease 1 (XRN1) (Kargutkar et al., 2023)."
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"Using Tet-promoter driven transcriptional pulsing approach and a β-globin reporter gene, it has been assessed that the deadenylation of mRNAs is a biphasic process in which the PAN2–PAN3 complex first[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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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 ."
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"The slight effect of PAN3 depletion on poly(A) tail length for EEF1G and RPS6 mRNAs could nevertheless be indicative of PAN2-PAN3 complex involvement in their deadenylation."
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"We demonstrated that ATF4 (activating transcription factor 4) mRNA corresponds to an endogenous model for biphasic deadenylation, with PAN2-PAN3 complex involved in the first step of deadenylation and[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Peak areas were calculated using the wand tool and, after surface density normalization, gel lane density profiles were superimposed.We first explored the effect of translation termination factor eRF3[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"These results indicate a protective effect of the termination factor eRF3a against ATF4 mRNA deadenylation and show that the deadenylation is initiated by the PAN2-PAN3 complex."
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"This result could be indicative that these mRNAs experienced another degradation process than the biphasic process initiated by PAN2-PAN3 complex, possibly a single step deadenylation process."
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"Only the global poly(A) tail length decrease with time is observable.The preferential protection of long-tailed ATF4 molecules in PAN3-depleted cells favored the view that deadenylation of ATF4 mRNA i[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"35 , 36 , 37 Three deadenylase complexes contribute to deadenylation activity in mammals, including the PARN, CCR4‐NOT complex and PAN2‐PAN3 complex, among which CCR4‐NOT complex is considered to play the major role."
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"Several findings suggest extensive redundancy between the Ccr4–Not and Pan2–Pan3 complexes in deadenylation of cytoplasmic mRNA."
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"No mouse models illuminating the role of the Pan2–Pan3 complex have been described to date."
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"25 The deadenylation process is triggered by deadenylases, which include the PARN, PAN2‐PAN3 complex and CCR4‐NOT complex in mammals."
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"mRNA deadenylation is catalysed by deadenylases such as the CCR4‐NOT complex, PAN2‐PAN3 complex and PARN."
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"In this case, the AGO protein without an endonucleolytic cleavage activity recruits the TNRC6 protein, which subsequently interacts with poly(A)-binding protein (PABP) and deadenylase complexes such as the PAN2-PAN3 complex and the CCR4-NOT complex (Jonas and Izaurralde 2015)."
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