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Rbfox Proteins Regulate Splicing as Part of a Large Multiprotein Complex LASR
- Source :
- Cell, vol 165, iss 3
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
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 toRbfox crosslinking sites invivo. These findings demonstrate that Rbfox proteins bind RNA with a defined set of cofactors and affect a broader set ofexons than previously recognized. The function of this multimeric LASR complex has implications for deciphering the regulatory codes controlling splicing networks.
- Subjects :
- 0301 basic medicine
Multiprotein complex
1.1 Normal biological development and functioning
RNA Splicing
viruses
RNA-binding protein
Biology
Medical and Health Sciences
Article
General Biochemistry, Genetics and Molecular Biology
Mice
03 medical and health sciences
chemistry.chemical_compound
Exon
Underpinning research
Genetics
RNA Precursors
Animals
Humans
3' Untranslated Regions
Cell Nucleus
DDX5
Alternative splicing
Intron
Brain
RNA-Binding Proteins
RNA
Exons
Biological Sciences
Introns
Cell biology
HEK293 Cells
030104 developmental biology
chemistry
Multiprotein Complexes
RNA splicing
Generic health relevance
Developmental Biology
Subjects
Details
- ISSN :
- 00928674
- Volume :
- 165
- Database :
- OpenAIRE
- Journal :
- Cell
- Accession number :
- edsair.doi.dedup.....c7a2292d929002795e34879f72539009