6yvh
CWC22-CWC27-EIF4A3 Complex
Structural highlights
FunctionCWC22_HUMAN Required for pre-mRNA splicing and for exon-junction complex (EJC) assembly. Hinders EIF4A3 from non-specifically binding RNA and escorts it to the splicing machinery to promote EJC assembly on mature mRNAs. Through its role in EJC assembly, required for nonsense-mediated mRNA decay.[1] [2] [3] Publication Abstract from PubMedHuman CWC27 is an uncharacterized splicing factor and mutations in its gene are linked to retinal degeneration and other developmental defects. We identify the splicing factor CWC22 as the major CWC27 partner. Both CWC27 and CWC22 are present in published Bact spliceosome structures, but no interacting domains are visible. Here, the structure of a CWC27/CWC22 heterodimer bound to the exon junction complex (EJC) core component eIF4A3 is solved at 3A-resolution. According to spliceosomal structures, the EJC is recruited in the C complex, once CWC27 has left. Our 3D structure of the eIF4A3/CWC22/CWC27 complex is compatible with the Bact spliceosome structure but not with that of the C complex, where a CWC27 loop would clash with the EJC core subunit Y14. A CWC27/CWC22 building block might thus form an intermediate landing platform for eIF4A3 onto the Bact complex prior to its conversion into C complex. Knock-down of either CWC27 or CWC22 in immortalized retinal pigment epithelial cells affects numerous common genes, indicating that these proteins cooperate, targeting the same pathways. As the most up-regulated genes encode factors involved in inflammation, our findings suggest a possible link to the retinal degeneration associated with CWC27 deficiencies. Structural and functional insights into CWC27/CWC22 heterodimer linking the exon junction complex to spliceosomes.,Busetto V, Barbosa I, Basquin J, Marquenet E, Hocq R, Hennion M, Paternina JA, Namane A, Conti E, Bensaude O, Le Hir H Nucleic Acids Res. 2020 Apr 24. pii: 5824608. doi: 10.1093/nar/gkaa267. PMID:32329775[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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