|
|
| (One intermediate revision not shown.) |
| Line 3: |
Line 3: |
| | <StructureSection load='6r9j' size='340' side='right'caption='[[6r9j]], [[Resolution|resolution]] 3.33Å' scene=''> | | <StructureSection load='6r9j' size='340' side='right'caption='[[6r9j]], [[Resolution|resolution]] 3.33Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6r9j]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6R9J OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6R9J FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6r9j]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] and [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6R9J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6R9J FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6r9i|6r9i]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.326Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Poly(A)-specific_ribonuclease Poly(A)-specific ribonuclease], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.13.4 3.1.13.4] </span></td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6r9j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6r9j OCA], [https://pdbe.org/6r9j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6r9j RCSB], [https://www.ebi.ac.uk/pdbsum/6r9j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6r9j ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6r9j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6r9j OCA], [http://pdbe.org/6r9j PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6r9j RCSB], [http://www.ebi.ac.uk/pdbsum/6r9j PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6r9j ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PAN2_YEAST PAN2_YEAST]] Catalytic subunit of the poly(A)-nuclease (PAN) deadenylation complex, one of two cytoplasmic mRNA deadenylases involved in mRNA turnover. PAN specifically shortens poly(A) tails of RNA when the poly(A) stretch is bound by poly(A)-binding protein PAB1, which is followed by rapid degradation of the shortened mRNA tails by the CCR4-NOT complex. Deadenylated mRNAs are then degraded by two alternative mechanisms, namely exosome-mediated 3'-5' exonucleolytic degradation, or deadenlyation-dependent mRNA decaping by DCP1-DCP2 and subsequent 5'-3' exonucleolytic degradation by XRN1. May also be involved in post-transcriptional maturation of mRNA poly(A) tails, trimming the tails from their synthesized length to the slightly shorter, apparently messenger-specific length found on newly exported mRNAs. PAN cooperates with protein kinase DUN1 in the regulation of RAD5 mRNA levels and cell survival in response to replicational stress.<ref>PMID:8550599</ref> <ref>PMID:1358757</ref> <ref>PMID:8816488</ref> <ref>PMID:9774670</ref> <ref>PMID:11239395</ref> <ref>PMID:11953437</ref> <ref>PMID:15630021</ref> <ref>PMID:15894541</ref> | + | [https://www.uniprot.org/uniprot/PAN2_YEAST PAN2_YEAST] Catalytic subunit of the poly(A)-nuclease (PAN) deadenylation complex, one of two cytoplasmic mRNA deadenylases involved in mRNA turnover. PAN specifically shortens poly(A) tails of RNA when the poly(A) stretch is bound by poly(A)-binding protein PAB1, which is followed by rapid degradation of the shortened mRNA tails by the CCR4-NOT complex. Deadenylated mRNAs are then degraded by two alternative mechanisms, namely exosome-mediated 3'-5' exonucleolytic degradation, or deadenlyation-dependent mRNA decaping by DCP1-DCP2 and subsequent 5'-3' exonucleolytic degradation by XRN1. May also be involved in post-transcriptional maturation of mRNA poly(A) tails, trimming the tails from their synthesized length to the slightly shorter, apparently messenger-specific length found on newly exported mRNAs. PAN cooperates with protein kinase DUN1 in the regulation of RAD5 mRNA levels and cell survival in response to replicational stress.<ref>PMID:8550599</ref> <ref>PMID:1358757</ref> <ref>PMID:8816488</ref> <ref>PMID:9774670</ref> <ref>PMID:11239395</ref> <ref>PMID:11953437</ref> <ref>PMID:15630021</ref> <ref>PMID:15894541</ref> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | The 3' poly(A) tail of messenger RNA is fundamental to regulating eukaryotic gene expression. Shortening of the poly(A) tail, termed deadenylation, reduces transcript stability and inhibits translation. Nonetheless, the mechanism for poly(A) recognition by the conserved deadenylase complexes Pan2-Pan3 and Ccr4-Not is poorly understood. Here we provide a model for poly(A) RNA recognition by two DEDD-family deadenylase enzymes, Pan2 and the Ccr4-Not nuclease Caf1. Crystal structures of Saccharomyces cerevisiae Pan2 in complex with RNA show that, surprisingly, Pan2 does not form canonical base-specific contacts. Instead, it recognizes the intrinsic stacked, helical conformation of poly(A) RNA. Using a fully reconstituted biochemical system, we show that disruption of this structure-for example, by incorporation of guanosine into poly(A)-inhibits deadenylation by both Pan2 and Caf1. Together, these data establish a paradigm for specific recognition of the conformation of poly(A) RNA by proteins that regulate gene expression. |
| | + | |
| | + | The intrinsic structure of poly(A) RNA determines the specificity of Pan2 and Caf1 deadenylases.,Tang TTL, Stowell JAW, Hill CH, Passmore LA Nat Struct Mol Biol. 2019 May 20. pii: 10.1038/s41594-019-0227-9. doi:, 10.1038/s41594-019-0227-9. PMID:31110294<ref>PMID:31110294</ref> |
| | + | |
| | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | + | </div> |
| | + | <div class="pdbe-citations 6r9j" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| Line 15: |
Line 23: |
| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Hill, C H]] | + | [[Category: Saccharomyces cerevisiae]] |
| - | [[Category: Passmore, L A]] | + | [[Category: Saccharomyces cerevisiae S288C]] |
| - | [[Category: Stowell, J A.W]] | + | [[Category: Hill CH]] |
| - | [[Category: Tang, T T.L]] | + | [[Category: Passmore LA]] |
| - | [[Category: Deadenylase]] | + | [[Category: Stowell JAW]] |
| - | [[Category: Dedd rnase]] | + | [[Category: Tang TTL]] |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Pseudoubiquitin hydrolase]]
| + | |
| Structural highlights
Function
PAN2_YEAST Catalytic subunit of the poly(A)-nuclease (PAN) deadenylation complex, one of two cytoplasmic mRNA deadenylases involved in mRNA turnover. PAN specifically shortens poly(A) tails of RNA when the poly(A) stretch is bound by poly(A)-binding protein PAB1, which is followed by rapid degradation of the shortened mRNA tails by the CCR4-NOT complex. Deadenylated mRNAs are then degraded by two alternative mechanisms, namely exosome-mediated 3'-5' exonucleolytic degradation, or deadenlyation-dependent mRNA decaping by DCP1-DCP2 and subsequent 5'-3' exonucleolytic degradation by XRN1. May also be involved in post-transcriptional maturation of mRNA poly(A) tails, trimming the tails from their synthesized length to the slightly shorter, apparently messenger-specific length found on newly exported mRNAs. PAN cooperates with protein kinase DUN1 in the regulation of RAD5 mRNA levels and cell survival in response to replicational stress.[1] [2] [3] [4] [5] [6] [7] [8]
Publication Abstract from PubMed
The 3' poly(A) tail of messenger RNA is fundamental to regulating eukaryotic gene expression. Shortening of the poly(A) tail, termed deadenylation, reduces transcript stability and inhibits translation. Nonetheless, the mechanism for poly(A) recognition by the conserved deadenylase complexes Pan2-Pan3 and Ccr4-Not is poorly understood. Here we provide a model for poly(A) RNA recognition by two DEDD-family deadenylase enzymes, Pan2 and the Ccr4-Not nuclease Caf1. Crystal structures of Saccharomyces cerevisiae Pan2 in complex with RNA show that, surprisingly, Pan2 does not form canonical base-specific contacts. Instead, it recognizes the intrinsic stacked, helical conformation of poly(A) RNA. Using a fully reconstituted biochemical system, we show that disruption of this structure-for example, by incorporation of guanosine into poly(A)-inhibits deadenylation by both Pan2 and Caf1. Together, these data establish a paradigm for specific recognition of the conformation of poly(A) RNA by proteins that regulate gene expression.
The intrinsic structure of poly(A) RNA determines the specificity of Pan2 and Caf1 deadenylases.,Tang TTL, Stowell JAW, Hill CH, Passmore LA Nat Struct Mol Biol. 2019 May 20. pii: 10.1038/s41594-019-0227-9. doi:, 10.1038/s41594-019-0227-9. PMID:31110294[9]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Boeck R, Tarun S Jr, Rieger M, Deardorff JA, Muller-Auer S, Sachs AB. The yeast Pan2 protein is required for poly(A)-binding protein-stimulated poly(A)-nuclease activity. J Biol Chem. 1996 Jan 5;271(1):432-8. PMID:8550599
- ↑ Lowell JE, Rudner DZ, Sachs AB. 3'-UTR-dependent deadenylation by the yeast poly(A) nuclease. Genes Dev. 1992 Nov;6(11):2088-99. PMID:1358757
- ↑ Brown CE, Tarun SZ Jr, Boeck R, Sachs AB. PAN3 encodes a subunit of the Pab1p-dependent poly(A) nuclease in Saccharomyces cerevisiae. Mol Cell Biol. 1996 Oct;16(10):5744-53. PMID:8816488
- ↑ Brown CE, Sachs AB. Poly(A) tail length control in Saccharomyces cerevisiae occurs by message-specific deadenylation. Mol Cell Biol. 1998 Nov;18(11):6548-59. PMID:9774670
- ↑ Tucker M, Valencia-Sanchez MA, Staples RR, Chen J, Denis CL, Parker R. The transcription factor associated Ccr4 and Caf1 proteins are components of the major cytoplasmic mRNA deadenylase in Saccharomyces cerevisiae. Cell. 2001 Feb 9;104(3):377-86. PMID:11239395
- ↑ Hammet A, Pike BL, Heierhorst J. Posttranscriptional regulation of the RAD5 DNA repair gene by the Dun1 kinase and the Pan2-Pan3 poly(A)-nuclease complex contributes to survival of replication blocks. J Biol Chem. 2002 Jun 21;277(25):22469-74. Epub 2002 Apr 12. PMID:11953437 doi:http://dx.doi.org/10.1074/jbc.M202473200
- ↑ Dunn EF, Hammell CM, Hodge CA, Cole CN. Yeast poly(A)-binding protein, Pab1, and PAN, a poly(A) nuclease complex recruited by Pab1, connect mRNA biogenesis to export. Genes Dev. 2005 Jan 1;19(1):90-103. PMID:15630021 doi:http://dx.doi.org/19/1/90
- ↑ Dheur S, Nykamp KR, Viphakone N, Swanson MS, Minvielle-Sebastia L. Yeast mRNA Poly(A) tail length control can be reconstituted in vitro in the absence of Pab1p-dependent Poly(A) nuclease activity. J Biol Chem. 2005 Jul 1;280(26):24532-8. Epub 2005 May 12. PMID:15894541 doi:http://dx.doi.org/M504720200
- ↑ Tang TTL, Stowell JAW, Hill CH, Passmore LA. The intrinsic structure of poly(A) RNA determines the specificity of Pan2 and Caf1 deadenylases. Nat Struct Mol Biol. 2019 May 20. pii: 10.1038/s41594-019-0227-9. doi:, 10.1038/s41594-019-0227-9. PMID:31110294 doi:http://dx.doi.org/10.1038/s41594-019-0227-9
|
