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| | <SX load='6g90' size='340' side='right' viewer='molstar' caption='[[6g90]], [[Resolution|resolution]] 4.00Å' scene=''> | | <SX load='6g90' size='340' side='right' viewer='molstar' caption='[[6g90]], [[Resolution|resolution]] 4.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6g90]] is a 38 chain structure with sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6G90 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6G90 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6g90]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6G90 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6G90 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]] 4Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=N:ANY+5-MONOPHOSPHATE+NUCLEOTIDE'>N</scene>, <scene name='pdbligand=PSU:PSEUDOURIDINE-5-MONOPHOSPHATE'>PSU</scene>, <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=N:ANY+5-MONOPHOSPHATE+NUCLEOTIDE'>N</scene>, <scene name='pdbligand=PSU:PSEUDOURIDINE-5-MONOPHOSPHATE'>PSU</scene>, <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=6g90 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6g90 OCA], [http://pdbe.org/6g90 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6g90 RCSB], [http://www.ebi.ac.uk/pdbsum/6g90 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6g90 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=6g90 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6g90 OCA], [https://pdbe.org/6g90 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6g90 RCSB], [https://www.ebi.ac.uk/pdbsum/6g90 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6g90 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/RU2A_YEAST RU2A_YEAST]] Involved in pre-mRNA splicing. Associates to U2 snRNA in a MSL1 dependent manner and is required for normal accumulation of U2 snRNA. Required for the spliceosome assembly and the efficient addition of U2 snRNP onto the pre-mRNA.<ref>PMID:9799242</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/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/RDS3_YEAST RDS3_YEAST]] Required for pre-mRNA splicing. Involved in regulation of drug sensitivity and may play a role in multidrug resistance.<ref>PMID:11943786</ref> <ref>PMID:14517302</ref> [[http://www.uniprot.org/uniprot/PRP9_YEAST PRP9_YEAST]] mRNA splicing factors, PRP9, PRP11, and PRP21, are necessary for binding of the U2 snRNP to the pre-mRNA in an early step of spliceosome assembly. [[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/HSH49_YEAST HSH49_YEAST]] Possible SF3b-like factor. [[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/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/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/RSE1_YEAST RSE1_YEAST]] Involved in G2/M transition (By similarity). Required for pre-mRNA splicing and endoplasmic reticulum (ER) to Golgi secretion pathway. U2 snRNPs associated protein required for the pre-spliceosome assembly. The involvement in ER to Golgi secretion is probably indirect and due to the splicing of the pre-mRNA coding for SAR1, a small GTP-binding protein required for COPII vesicle formation from the ER.<ref>PMID:10369685</ref> <ref>PMID:9819400</ref> [[http://www.uniprot.org/uniprot/PRP21_YEAST PRP21_YEAST]] mRNA splicing factors, PRP9, PRP11, and PRP21, are necessary for binding of the U2 snRNP to the pre-mRNA in an early step of spliceosome assembly. [[http://www.uniprot.org/uniprot/YSF3_YEAST YSF3_YEAST]] Involved in pre-mRNA splicing. Required for the SF3b integrity and prespliceosome assembly.<ref>PMID:16314500</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/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/SF3B1_YEAST SF3B1_YEAST]] Contacts pre-mRNA on both sides of the branch site early in spliceosome assembly. [[http://www.uniprot.org/uniprot/MSL1_YEAST MSL1_YEAST]] Involved in pre-mRNA splicing. This protein is associated with snRNP U2. It binds stem loop IV of U2 snRNA.<ref>PMID:8649387</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/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. [[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/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/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/CUS1_YEAST CUS1_YEAST]] Essential splicing protein required for U2 snRNP binding to pre-mRNA during spliceosome assembly. [[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/RU17_YEAST RU17_YEAST]] Involved in nuclear mRNA splicing. [[http://www.uniprot.org/uniprot/PRP11_YEAST PRP11_YEAST]] mRNA splicing factors, PRP9, PRP11, and PRP21, are necessary for addition of the U2 snRNP to the pre-mRNA in an early step of spliceosome assembly.<ref>PMID:9710584</ref> [[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> | + | [https://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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | | | |
| | ==See Also== | | ==See Also== |
| | + | *[[Increased sodium tolerance protein|Increased sodium tolerance protein]] |
| | + | *[[Nucleoprotein 3D structures|Nucleoprotein 3D structures]] |
| | *[[Pre-mRNA splicing factors 3D structures|Pre-mRNA splicing factors 3D structures]] | | *[[Pre-mRNA splicing factors 3D structures|Pre-mRNA splicing factors 3D structures]] |
| | + | *[[Sm-like protein 3D structures|Sm-like protein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| | [[Category: Saccharomyces cerevisiae]] | | [[Category: Saccharomyces cerevisiae]] |
| - | [[Category: Charenton, C]] | + | [[Category: Charenton C]] |
| - | [[Category: Lin, P C]] | + | [[Category: Lin P-C]] |
| - | [[Category: Nagai, K]] | + | [[Category: Nagai K]] |
| - | [[Category: Plaschka, C]] | + | [[Category: Plaschka C]] |
| - | [[Category: A complex]]
| + | |
| - | [[Category: Rna processing]]
| + | |
| - | [[Category: Rna-protein complex]]
| + | |
| - | [[Category: Spliceosome]]
| + | |
| - | [[Category: Splicing]]
| + | |
| Structural highlights
Function
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.[1] [2]
Publication Abstract from PubMed
The spliceosome catalyses the excision of introns from pre-mRNA in two steps, branching and exon ligation, and is assembled from five small nuclear ribonucleoprotein particles (snRNPs; U1, U2, U4, U5, U6) and numerous non-snRNP factors(1). For branching, the intron 5' splice site and the branch point sequence are selected and brought by the U1 and U2 snRNPs into the prespliceosome(1), which is a focal point for regulation by alternative splicing factors(2). The U4/U6.U5 tri-snRNP subsequently joins the prespliceosome to form the complete pre-catalytic spliceosome. Recent studies have revealed the structural basis of the branching and exon-ligation reactions(3), however, the structural basis of the early events in spliceosome assembly remains poorly understood(4). Here we report the cryo-electron microscopy structure of the yeast Saccharomyces cerevisiae prespliceosome at near-atomic resolution. The structure reveals an induced stabilization of the 5' splice site in the U1 snRNP, and provides structural insights into the functions of the human alternative splicing factors LUC7-like (yeast Luc7) and TIA-1 (yeast Nam8), both of which have been linked to human disease(5,6). In the prespliceosome, the U1 snRNP associates with the U2 snRNP through a stable contact with the U2 3' domain and a transient yeast-specific contact with the U2 SF3b-containing 5' region, leaving its tri-snRNP-binding interface fully exposed. The results suggest mechanisms for 5' splice site transfer to the U6 ACAGAGA region within the assembled spliceosome and for its subsequent conversion to the activation-competent B-complex spliceosome(7,8). Taken together, the data provide a working model to investigate the early steps of spliceosome assembly.
Prespliceosome structure provides insights into spliceosome assembly and regulation.,Plaschka C, Lin PC, Charenton C, Nagai K Nature. 2018 Jul;559(7714):419-422. doi: 10.1038/s41586-018-0323-8. Epub 2018 Jul, 11. PMID:29995849[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Liao XC, Tang J, Rosbash M. An enhancer screen identifies a gene that encodes the yeast U1 snRNP A protein: implications for snRNP protein function in pre-mRNA splicing. Genes Dev. 1993 Mar;7(3):419-28. PMID:8449403
- ↑ Tang J, Rosbash M. Characterization of yeast U1 snRNP A protein: identification of the N-terminal RNA binding domain (RBD) binding site and evidence that the C-terminal RBD functions in splicing. RNA. 1996 Oct;2(10):1058-70. PMID:8849781
- ↑ Plaschka C, Lin PC, Charenton C, Nagai K. Prespliceosome structure provides insights into spliceosome assembly and regulation. Nature. 2018 Jul;559(7714):419-422. doi: 10.1038/s41586-018-0323-8. Epub 2018 Jul, 11. PMID:29995849 doi:http://dx.doi.org/10.1038/s41586-018-0323-8
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