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.
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