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CWC22 connects pre-mRNA splicing and exon junction complex assembly.

Authors
  • Steckelberg, Anna-Lena1
  • Boehm, Volker
  • Gromadzka, Agnieszka M
  • Gehring, Niels H
  • 1 University of Cologne, Institute for Genetics, Cologne, Germany. , (Germany)
Type
Published Article
Journal
Cell Reports
Publisher
Elsevier
Publication Date
Sep 27, 2012
Volume
2
Issue
3
Pages
454–461
Identifiers
DOI: 10.1016/j.celrep.2012.08.017
PMID: 22959432
Source
Medline
Language
English
License
Unknown

Abstract

The exon junction complex (EJC) is a key regulator of posttranscriptional mRNA fate and binds to mRNA during splicing. Although the composition of EJCs is well understood, the mechanism mediating splicing-dependent EJC assembly and the factor(s) recruiting the EJC remain elusive. Here, we identify CWC22 as an essential splicing factor that is required for EJC assembly. In CWC22-depleted cells, pre-mRNA splicing is impaired but is rescued by a central fragment of CWC22. We show that the MIF4G domain of CWC22 initiates EJC assembly via a direct interaction with the EJC core protein eIF4A3, and we characterize mutations in eIF4A3 that abolish binding to CWC22. These eIF4A3 mutants efficiently nucleate splicing-independent recombinant EJC core complexes, but they fail to support splicing-dependent EJC deposition. Our work establishes a direct link between the splicing machinery and the EJC, hence uncovering a molecular interaction at the center of a posttranscriptional gene regulation network. Copyright © 2012 The Authors. Published by Elsevier Inc. All rights reserved.

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