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Cell. 2016 Apr 21;165(3):606-19. doi: 10.1016/j.cell.2016.03.040.

Rbfox Proteins Regulate Splicing as Part of a Large Multiprotein Complex LASR.

Author information

  • 1Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • 2Molecular Biology Interdepartmental Ph.D. Program, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • 3Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • 4Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: dougb@microbio.ucla.edu.

Abstract

Rbfox proteins control alternative splicing and posttranscriptional regulation in mammalian brain and are implicated in neurological disease. These proteins recognize the RNA sequence (U)GCAUG, but their structures and diverse roles imply a variety of protein-protein interactions. We find that nuclear Rbfox proteins are bound within a large assembly of splicing regulators (LASR), a multimeric complex containing the proteins hnRNP M, hnRNP H, hnRNP C, Matrin3, NF110/NFAR-2, NF45, and DDX5, all approximately equimolar to Rbfox. We show that splicing repression mediated by hnRNP M is stimulated by Rbfox. Virtually all the intron-bound Rbfox is associated with LASR, and hnRNP M motifs are enriched adjacent to Rbfox crosslinking sites in vivo. These findings demonstrate that Rbfox proteins bind RNA with a defined set of cofactors and affect a broader set of exons than previously recognized. The function of this multimeric LASR complex has implications for deciphering the regulatory codes controlling splicing networks.

PMID:
27104978
PMCID:
PMC4841943
[Available on 2017-04-21]
DOI:
10.1016/j.cell.2016.03.040
[PubMed - indexed for MEDLINE]
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