Structural and functional insights into CWC27/CWC22 heterodimer linking the exon junction complex to spliceosomes.
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
04 06 2020
04 06 2020
Historique:
accepted:
22
04
2020
revised:
01
04
2020
received:
13
02
2020
pubmed:
25
4
2020
medline:
18
8
2020
entrez:
25
4
2020
Statut:
ppublish
Résumé
Human 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 3Å-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.
Identifiants
pubmed: 32329775
pii: 5824608
doi: 10.1093/nar/gkaa267
pmc: PMC7261170
doi:
Substances chimiques
CWC22 protein, human
0
RNA-Binding Proteins
0
Eukaryotic Initiation Factor-4A
EC 2.7.7.-
Cwc27 protein, human
EC 5.2.1.-
Cyclophilins
EC 5.2.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5670-5683Informations de copyright
© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.
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