Isolated pseudo-RNA-recognition motifs of SR proteins can regulate splicing using a noncanonical mode of RNA recognition

Cléry, A., Sinha, R., Anczuków, O., Corrionero, A., Moursy, A., Daubner, G. M., Valcárcel, J., Krainer, A. R., Allain, F. H. T. (July 2013) Isolated pseudo-RNA-recognition motifs of SR proteins can regulate splicing using a noncanonical mode of RNA recognition. Proceedings of the National Academy of Sciences of the United States of America, 110 (30). E2802-E2811. ISSN 00278424

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Abstract

Serine/arginine (SR) proteins, one of the major families of alternativesplicing regulators in Eukarya, have two types of RNA-recognition motifs (RRMs): a canonical RRM and a pseudo-RRM. Although pseudo-RRMs are crucial for activity of SR proteins, their mode of action was unknown. By solving the structure of the human SRSF1 pseudo-RRM bound to RNA, we discovered a very unusual and sequence-specific RNA-binding mode that is centered on one a-helix and does not involve the β-sheet surface, which typically mediates RNA binding by RRMs. Remarkably, this mode of binding is conserved in all pseudo-RRMs tested. Furthermore, the isolated pseudo- RRM is sufficient to regulate splicing of about half of the SRSF1 target genes tested, and the bound a-helix is a pivotal element for this function. Our results strongly suggest that SR proteins with a pseudo-RRM frequently regulate splicing by competing with, rather than recruiting, spliceosome components, using solely this unusual RRM.

Item Type:	Paper
Uncontrolled Keywords:	NMR Protein-RNA complex Splicing factor
Subjects:	bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > RNA expression bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > splicing factor
CSHL Authors:	Anczukow, Olga Krainer, Adrian R. Sinha, Rahul
Communities:	CSHL Cancer Center Program > Gene Regulation and Cell Proliferation CSHL Cancer Center Shared Resources > Genetic Screening Service CSHL labs > Krainer lab CSHL Cancer Center Shared Resources > Functional Genomics and Genetics Service
Depositing User:	Matt Covey
Date:	23 July 2013
Date Deposited:	16 Aug 2013 19:19
Last Modified:	22 Dec 2017 16:24
PMCID:	PMC3725064
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/28542

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