| Structural highlights
7w5a is a 18 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | Electron Microscopy, Resolution 3.6Å |
| Ligands: | , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
RBM22_HUMAN Involved in the first step of pre-mRNA splicing. Binds directly to the internal stem-loop (ISL) domain of the U6 snRNA and to the pre-mRNA intron near the 5' splice site during the activation and catalytic phases of the spliceosome cycle. Involved in both translocations of the nuclear SLU7 to the cytoplasm and the cytosolic calcium-binding protein PDCD6 to the nucleus upon cellular stress responses.[1] [2] [3]
Publication Abstract from PubMed
Pre-mRNA splicing involves two sequential reactions: branching and exon ligation. The C complex after branching undergoes remodeling to become the C( *) complex, which executes exon ligation. Here, we report cryo-EM structures of two intermediate human spliceosomal complexes, pre-C( *)-I and pre-C( *)-II, both at 3.6 A. In both structures, the 3' splice site is already docked into the active site, the ensuing 3' exon sequences are anchored on PRP8, and the step II factor FAM192A contacts the duplex between U2 snRNA and the branch site. In the transition of pre-C( *)-I to pre-C( *)-II, the step II factors Cactin, FAM32A, PRKRIP1, and SLU7 are recruited. Notably, the RNA helicase PRP22 is positioned quite differently in the pre-C( *)-I, pre-C( *)-II, and C( *) complexes, suggesting a role in 3' exon binding and proofreading. Together with information on human C and C( *) complexes, our studies recapitulate a molecular choreography of the C-to-C( *) transition, revealing mechanistic insights into exon ligation.
Mechanism of exon ligation by human spliceosome.,Zhan X, Lu Y, Zhang X, Yan C, Shi Y Mol Cell. 2022 Aug 4;82(15):2769-2778.e4. doi: 10.1016/j.molcel.2022.05.021. Epub , 2022 Jun 14. PMID:35705093[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Montaville P, Dai Y, Cheung CY, Giller K, Becker S, Michalak M, Webb SE, Miller AL, Krebs J. Nuclear translocation of the calcium-binding protein ALG-2 induced by the RNA-binding protein RBM22. Biochim Biophys Acta. 2006 Nov;1763(11):1335-43. Epub 2006 Sep 14. PMID:17045351 doi:http://dx.doi.org/10.1016/j.bbamcr.2006.09.003
- ↑ Janowicz A, Michalak M, Krebs J. Stress induced subcellular distribution of ALG-2, RBM22 and hSlu7. Biochim Biophys Acta. 2011 May;1813(5):1045-9. doi: 10.1016/j.bbamcr.2010.11.010., Epub 2010 Nov 29. PMID:21122810 doi:http://dx.doi.org/10.1016/j.bbamcr.2010.11.010
- ↑ Rasche N, Dybkov O, Schmitzova J, Akyildiz B, Fabrizio P, Luhrmann R. Cwc2 and its human homologue RBM22 promote an active conformation of the spliceosome catalytic centre. EMBO J. 2012 Mar 21;31(6):1591-604. doi: 10.1038/emboj.2011.502. Epub 2012 Jan, 13. PMID:22246180 doi:http://dx.doi.org/10.1038/emboj.2011.502
- ↑ Zhan X, Lu Y, Zhang X, Yan C, Shi Y. Mechanism of exon ligation by human spliceosome. Mol Cell. 2022 Aug 4;82(15):2769-2778.e4. PMID:35705093 doi:10.1016/j.molcel.2022.05.021
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