View source for 9zec


==Cryo-EM structure of the endogenous U2/branchpoint spliceosomal complex (SF3A state 1)==
<StructureSection load='9zec' size='340' side='right'caption='[[9zec]], [[Resolution|resolution]] 3.61&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9zec]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9ZEC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9ZEC FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.61&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=OMC:O2-METHYLYCYTIDINE-5-MONOPHOSPHATE'>OMC</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'>[https://proteopedia.org/fgij/fg.htm?mol=9zec FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9zec OCA], [https://pdbe.org/9zec PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9zec RCSB], [https://www.ebi.ac.uk/pdbsum/9zec PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9zec ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RBM5_HUMAN RBM5_HUMAN] Component of the spliceosome A complex. Regulates alternative splicing of a number of mRNAs. May modulate splice site pairing after recruitment of the U1 and U2 snRNPs to the 5' and 3' splice sites of the intron. May both positively and negatively regulate aopotosis by regulating the alternative splicing of several genes involved in this process, including FAS and CASP2/caspase-2. In the case of FAS, promotes exclusion of exon 6 thereby producing a soluble form of FAS that inhibits apoptosis. In the case of CASP2/caspase-2, promotes exclusion of exon 9 thereby producing a catalytically active form of CASP2/Caspase-2 that induces apoptosis.<ref>PMID:10949932</ref> <ref>PMID:12207175</ref> <ref>PMID:12581154</ref> <ref>PMID:15192330</ref> <ref>PMID:16585163</ref> <ref>PMID:18851835</ref> <ref>PMID:18840686</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Pre-mRNA splicing determines the expressed proteome and is frequently dysregulated in cancer. The tumour-suppressor RBM5 controls an exon network regulating apoptosis, yet its molecular mechanism is elusive. Using in vivo spliceosome capture and cryogenic electron microscopy, we determined structures of precatalytic spliceosomes arrested by RBM5 immediately after U2 snRNP branchpoint recognition. Despite intron diversity, the U2-pre-mRNA duplex, branchpoint adenine, and downstream polypyrimidine tract are well-resolved. RBM5 binds the outer SF3B1 HEAT surface and performs dual functions: First, its helix-loop-helix motif and upstream zinc-finger domain sterically block tri-snRNP and Prp8 docking and prevent progression to pre-B and B(act) complexes; Second, its G-patch activates DHX15 and places this DExH-box helicase on the pre-mRNA as it exits SF3B1, poised for branch helix unwinding. DHX15 binding to SF3B1 is facilitated by U2SURP/SR140, which engages SF3B1 near RBM5's helix-loop-helix. Functional assays confirm that disruption of the RBM5 interfaces with either DHX15 or SF3B1 inhibit exon repression. Mutations at these regulatory interfaces are common in cancer genomes and predicted to disrupt its regulation of apoptotic isoforms. Thus, RBM5 acts as a dual-action spliceosome gatekeeper that couples helicase activation with physical stalling to enforce tumour-suppressive alternative splicing programmes.

The tumour suppressor RBM5 activates the helicase DHX15 to regulate splicing.,Liu S, Su T, Huang J, Lin CH, Black DL, Damianov A, Zhou ZH bioRxiv [Preprint]. 2026 Mar 27:2026.03.26.714623. doi: , 10.64898/2026.03.26.714623. PMID:41929118<ref>PMID:41929118</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9zec" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Liu S]]
[[Category: Su T]]
[[Category: Zhou ZH]]