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| | ==Solution structure of U1-A RRM2 (190-282)== | | ==Solution structure of U1-A RRM2 (190-282)== |
| - | <StructureSection load='7aep' size='340' side='right'caption='[[7aep]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='7aep' size='340' side='right'caption='[[7aep]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[7aep]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AEP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AEP FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7aep]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AEP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AEP FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2u1a|2u1a]]</div></td></tr> | + | </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=7aep FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7aep OCA], [https://pdbe.org/7aep PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7aep RCSB], [https://www.ebi.ac.uk/pdbsum/7aep PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7aep ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SNRPA ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7aep FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7aep OCA], [https://pdbe.org/7aep PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7aep RCSB], [https://www.ebi.ac.uk/pdbsum/7aep PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7aep ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/SNRPA_HUMAN SNRPA_HUMAN]] Binds stem loop II of U1 snRNA. 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. In a snRNP-free form (SF-A) may be involved in coupled pre-mRNA splicing and polyadenylation process. Binds preferentially to the 5'-UGCAC-3' motif in vitro.<ref>PMID:9848648</ref>
| + | [https://www.uniprot.org/uniprot/SNRPA_HUMAN SNRPA_HUMAN] Binds stem loop II of U1 snRNA. 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. In a snRNP-free form (SF-A) may be involved in coupled pre-mRNA splicing and polyadenylation process. Binds preferentially to the 5'-UGCAC-3' motif in vitro.<ref>PMID:9848648</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Allain, F H]] | + | [[Category: Allain FH]] |
| - | [[Category: Campagne, S]] | + | [[Category: Campagne S]] |
| - | [[Category: Rrm]]
| + | |
| - | [[Category: Splicing]]
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| - | [[Category: U1 snrnp tail]]
| + | |
| Structural highlights
Function
SNRPA_HUMAN Binds stem loop II of U1 snRNA. 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. In a snRNP-free form (SF-A) may be involved in coupled pre-mRNA splicing and polyadenylation process. Binds preferentially to the 5'-UGCAC-3' motif in vitro.[1]
Publication Abstract from PubMed
U1 small nuclear ribonucleoparticle (U1 snRNP) plays a central role during RNA processing. Previous structures of U1 snRNP revealed how the ribonucleoparticle is organized and recognizes the pre-mRNA substrate at the exon-intron junction. As with many other ribonucleoparticles involved in RNA metabolism, U1 snRNP contains extensions made of low complexity sequences. Here, we developed a protocol to reconstitute U1 snRNP in vitro using mostly full-length components in order to perform liquid-state NMR spectroscopy. The accuracy of the reconstitution was validated by probing the shape and structure of the particle by SANS and cryo-EM. Using an NMR spectroscopy-based approach, we probed, for the first time, the U1 snRNP tails at atomic detail and our results confirm their high degree of flexibility. We also monitored the labile interaction between the splicing factor PTBP1 and U1 snRNP and validated the U1 snRNA stem loop 4 as a binding site for the splicing regulator on the ribonucleoparticle. Altogether, we developed a method to probe the intrinsically disordered regions of U1 snRNP and map the interactions controlling splicing regulation. This approach could be used to get insights into the molecular mechanisms of alternative splicing and screen for potential RNA therapeutics.
An in vitro reconstituted U1 snRNP allows the study of the disordered regions of the particle and the interactions with proteins and ligands.,Campagne S, de Vries T, Malard F, Afanasyev P, Dorn G, Dedic E, Kohlbrecher J, Boehringer D, Clery A, Allain FH Nucleic Acids Res. 2021 Mar 2. pii: 6157091. doi: 10.1093/nar/gkab135. PMID:33677607[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lutz CS, Cooke C, O'Connor JP, Kobayashi R, Alwine JC. The snRNP-free U1A (SF-A) complex(es): identification of the largest subunit as PSF, the polypyrimidine-tract binding protein-associated splicing factor. RNA. 1998 Dec;4(12):1493-9. PMID:9848648
- ↑ Campagne S, de Vries T, Malard F, Afanasyev P, Dorn G, Dedic E, Kohlbrecher J, Boehringer D, Clery A, Allain FH. An in vitro reconstituted U1 snRNP allows the study of the disordered regions of the particle and the interactions with proteins and ligands. Nucleic Acids Res. 2021 Mar 2. pii: 6157091. doi: 10.1093/nar/gkab135. PMID:33677607 doi:http://dx.doi.org/10.1093/nar/gkab135
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