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

Proc Natl Acad Sci U S A. 2013 Jul 23;110(30):E2802-11. doi: 10.1073/pnas.1303445110. Epub 2013 Jul 8.


Serine/arginine (SR) proteins, one of the major families of alternative-splicing 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 α-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 α-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.

Keywords: NMR; protein–RNA complex; splicing factor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Arginine / chemistry*
  • Binding Sites
  • Models, Molecular
  • Molecular Sequence Data
  • Proteins / chemistry
  • Proteins / metabolism*
  • RNA / metabolism*
  • RNA Splicing*
  • Serine / chemistry*


  • Proteins
  • Serine
  • RNA
  • Arginine

Associated data

  • PDB/2M8D