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| <SX load='6n7p' size='340' side='right' viewer='molstar' caption='[[6n7p]], [[Resolution|resolution]] 3.60Å' scene=''> | | <SX load='6n7p' size='340' side='right' viewer='molstar' caption='[[6n7p]], [[Resolution|resolution]] 3.60Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
- | <table><tr><td colspan='2'>[[6n7p]] is a 21 chain structure with sequence from [http://en.wikipedia.org/wiki/Baker's_yeast Baker's yeast] and [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_(strain_atcc_204508_/_s288c) Saccharomyces cerevisiae (strain atcc 204508 / s288c)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6N7P OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6N7P FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6n7p]] is a 10 chain structure with sequence from [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=6N7P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6N7P FirstGlance]. <br> |
- | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.6Å</td></tr> |
- | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=UNK:UNKNOWN'>UNK</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
- | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6n7p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6n7p OCA], [http://pdbe.org/6n7p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6n7p RCSB], [http://www.ebi.ac.uk/pdbsum/6n7p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6n7p ProSAT]</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=6n7p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6n7p OCA], [https://pdbe.org/6n7p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6n7p RCSB], [https://www.ebi.ac.uk/pdbsum/6n7p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6n7p ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Function == | | == Function == |
- | [[http://www.uniprot.org/uniprot/RSMB_YEAST RSMB_YEAST]] Involved in pre-mRNA splicing. Binds snRNA U1, U2, U4 and U5 which contain a highly conserved structural motif called the Sm binding site. [[http://www.uniprot.org/uniprot/NCBP2_YEAST NCBP2_YEAST]] Component of the CBC complex, which binds co-transcriptionally to the cap of pre-mRNAs and is involved in maturation, export and degradation of nuclear mRNAs. The CBC complex is required for efficient pre-mRNA splicing through efficient commitment complex and spliceosome formation. Together with NPL3, the CBC complex is required for export of mRNAs out of the nucleus. The CBC complex is also involved in nuclear mRNA degradation, probably by directing the mRNAs to the sites of degradation. Affects replication of the positive-strand RNA virus BMV.<ref>PMID:10490594</ref> <ref>PMID:10823828</ref> <ref>PMID:12756324</ref> <ref>PMID:14671320</ref> <ref>PMID:15753296</ref> <ref>PMID:16166263</ref> <ref>PMID:8682299</ref> <ref>PMID:8811086</ref> <ref>PMID:8858145</ref> <ref>PMID:9215889</ref> [[http://www.uniprot.org/uniprot/SNU56_YEAST SNU56_YEAST]] Component of the U1 snRNP particle, which recognizes and binds the 5'-splice site of pre-mRNA. Together with other non-snRNP factors, U1 snRNP forms the spliceosomal commitment complex, that targets pre-mRNA to the splicing pathway. [[http://www.uniprot.org/uniprot/RU1C_YEAST RU1C_YEAST]] Component of the spliceosomal U1 snRNP, which is essential for recognition of the pre-mRNA 5' splice-site and the subsequent assembly of the spliceosome. YHC1/U1-C is directly involved in initial 5' splice-site recognition for both constitutive and regulated alternative splicing. The interaction with the 5' splice-site seems to precede base-pairing between the pre-mRNA and the U1 snRNA. Stimulates commitment or early (E) complex formation by stabilizing the base pairing of the 5' end of the U1 snRNA and the 5' splice-site region.<ref>PMID:10072386</ref> <ref>PMID:12214237</ref> <ref>PMID:9233817</ref> [[http://www.uniprot.org/uniprot/RUXG_YEAST RUXG_YEAST]] Involved in pre-mRNA splicing. Binds snRNA U1, U2, U4 and U5 which contain a highly conserved structural motif called the Sm binding site. [[http://www.uniprot.org/uniprot/RU17_YEAST RU17_YEAST]] Involved in nuclear mRNA splicing. [[http://www.uniprot.org/uniprot/SMD2_YEAST SMD2_YEAST]] Involved in pre-mRNA splicing. Binds snRNA U1, U2, U4 and U5 which contain a highly conserved structural motif called the Sm binding site. [[http://www.uniprot.org/uniprot/RUXF_YEAST RUXF_YEAST]] Involved in pre-mRNA splicing. Binds snRNA U1, U2, U4 and U5 which contain a highly conserved structural motif called the Sm binding site. [[http://www.uniprot.org/uniprot/NAM8_YEAST NAM8_YEAST]] Acts as a suppressor of mitochondrial splicing deficiencies when overexpressed. Could be a non-essential component of the mitochondrial splicing machinery. [[http://www.uniprot.org/uniprot/RU1A_YEAST RU1A_YEAST]] Involved in nuclear mRNA splicing. The principal role of the U1A is to help fold or maintain U1 RNA in an active configuration. It is the first snRNP to interact with pre-mRNA. This interaction is required for the subsequent binding of U2 snRNP and the U4/U6/U5 tri-snRNP.<ref>PMID:8449403</ref> <ref>PMID:8849781</ref> [[http://www.uniprot.org/uniprot/LUC7_YEAST LUC7_YEAST]] Component of the U1 snRNP particle, which recognizes and binds the 5'-splice site of pre-mRNA. Together with other non-snRNP factors, U1 snRNP forms the spliceosomal commitment complex, that targets pre-mRNA to the splicing pathway.<ref>PMID:10500099</ref> <ref>PMID:10533282</ref> [[http://www.uniprot.org/uniprot/SMD1_YEAST SMD1_YEAST]] Involved in pre-mRNA splicing. Binds snRNA U1, U2, U4 and U5 which contain a highly conserved structural motif called the Sm binding site. Also binds telomerase RNA and is required for its accumulation.<ref>PMID:10490028</ref> <ref>PMID:8430095</ref> [[http://www.uniprot.org/uniprot/SMD3_YEAST SMD3_YEAST]] Involved in pre-mRNA splicing. Binds snRNA U1, U2, U4 and U5 which contain a highly conserved structural motif called the Sm binding site. Also binds telomerase RNA and is required for its accumulation.<ref>PMID:10490028</ref> <ref>PMID:7799953</ref> [[http://www.uniprot.org/uniprot/RUXE_YEAST RUXE_YEAST]] Involved in pre-mRNA splicing. Binds and is required for the stability of snRNA U1, U2, U4 and U5 which contain a highly conserved structural motif called the Sm binding site. Involved in cap modification.<ref>PMID:8918241</ref> [[http://www.uniprot.org/uniprot/NCBP1_YEAST NCBP1_YEAST]] Component of the CBC complex, which binds co-transcriptionally to the 5'-cap of pre-mRNAs and is involved in maturation, export and degradation of nuclear mRNAs. The CBC complex is required for efficient pre-mRNA splicing through efficient commitment complex and spliceosome formation. Together with NPL3, the CBC complex is required for export of mRNAs out of the nucleus. The CBC complex is also involved in nuclear mRNA degradation, probably by directing the mRNAs to the sites of degradation. Affects replication of the positive-strand RNA virus BMV.<ref>PMID:10490594</ref> <ref>PMID:10733586</ref> <ref>PMID:10823828</ref> <ref>PMID:12756324</ref> <ref>PMID:12897126</ref> <ref>PMID:14671320</ref> <ref>PMID:1512188</ref> <ref>PMID:15753296</ref> <ref>PMID:16166263</ref> <ref>PMID:8811086</ref> <ref>PMID:8846890</ref> <ref>PMID:8858145</ref> <ref>PMID:9499403</ref> [[http://www.uniprot.org/uniprot/SNU71_YEAST SNU71_YEAST]] Component of the U1 snRNP particle, which recognizes and binds the 5'-splice site of pre-mRNA. Together with other non-snRNP factors, U1 snRNP forms the spliceosomal commitment complex, that targets pre-mRNA to the splicing pathway.<ref>PMID:11877437</ref> [[http://www.uniprot.org/uniprot/PRP42_YEAST PRP42_YEAST]] Essential component of the U1 snRNP particle, which recognizes and binds the 5'-splice site of pre-mRNA. Together with other non-snRNP factors, U1 snRNP forms the spliceosomal commitment complex, that targets pre-mRNA to the splicing pathway. U1 snRNP is cotranscriptionally recruited to intron-containing genes. Required for U1 snRNP biogenesis.<ref>PMID:12897147</ref> <ref>PMID:9418882</ref> [[http://www.uniprot.org/uniprot/PRP40_YEAST PRP40_YEAST]] Required for pre-spliceosome formation, which is the first step of pre-mRNA splicing. This protein is associated with snRNP U1. Two commitment complexes, CC1 and CC2, have been defined in yeast. CC1 is a basal complex dependent only on the 5' splice site. CC2 is a complex of lower mobility and is dependent on a branchpoint as well as a 5' splice site region. This protein is involved in CC2 formation where it binds to the branchpoint binding protein MSL5, bridging the U1 snRNP-associated 5' splice site and the MSL5-associated branch point 3' intron splice site.<ref>PMID:9150140</ref> <ref>PMID:10978320</ref> <ref>PMID:15020406</ref> [[http://www.uniprot.org/uniprot/PRP39_YEAST PRP39_YEAST]] Function prior to stable branch point recognition by the U1 snRNP particle to facilitate or stabilize the U1 snRNP/5'-splice site interaction. Has a direct role in the assembly or function of a catalytically active spliceosome. | + | [https://www.uniprot.org/uniprot/RU17_YEAST RU17_YEAST] Involved in nuclear mRNA splicing. |
- | <div style="background-color:#fffaf0;">
| + | |
- | == Publication Abstract from PubMed ==
| + | |
- | The molecular mechanisms of exon definition and back-splicing are fundamental unanswered questions in pre-mRNA splicing. Here we report cryo-electron microscopy structures of the yeast spliceosomal E complex assembled on introns, providing a view of the earliest event in the splicing cycle that commits pre-mRNAs to splicing. The E complex architecture suggests that the same spliceosome can assemble across an exon, and that it either remodels to span an intron for canonical linear splicing (typically on short exons) or catalyses back-splicing to generate circular RNA (on long exons). The model is supported by our experiments, which show that an E complex assembled on the middle exon of yeast EFM5 or HMRA1 can be chased into circular RNA when the exon is sufficiently long. This simple model unifies intron definition, exon definition, and back-splicing through the same spliceosome in all eukaryotes and should inspire experiments in many other systems to understand the mechanism and regulation of these processes.
| + | |
| | | |
- | A unified mechanism for intron and exon definition and back-splicing.,Li X, Liu S, Zhang L, Issaian A, Hill RC, Espinosa S, Shi S, Cui Y, Kappel K, Das R, Hansen KC, Zhou ZH, Zhao R Nature. 2019 Sep;573(7774):375-380. doi: 10.1038/s41586-019-1523-6. Epub 2019 Sep, 4. PMID:31485080<ref>PMID:31485080</ref>
| + | ==See Also== |
- | | + | *[[Nucleoprotein 3D structures|Nucleoprotein 3D structures]] |
- | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | *[[Sm-like protein 3D structures|Sm-like protein 3D structures]] |
- | </div>
| + | |
- | <div class="pdbe-citations 6n7p" style="background-color:#fffaf0;"></div>
| + | |
- | == References ==
| + | |
- | <references/>
| + | |
| __TOC__ | | __TOC__ |
| </SX> | | </SX> |
- | [[Category: Baker's yeast]] | |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
- | [[Category: Li, X]] | + | [[Category: Saccharomyces cerevisiae S288C]] |
- | [[Category: Liu, S]] | + | [[Category: Li X]] |
- | [[Category: Zhao, R]] | + | [[Category: Liu S]] |
- | [[Category: Zhou, Z H]] | + | [[Category: Zhao R]] |
- | [[Category: E complex]]
| + | [[Category: Zhou ZH]] |
- | [[Category: Pre-mrna splicing]]
| + | |
- | [[Category: Rna binding protein]]
| + | |
- | [[Category: Spliceosome]]
| + | |