A peptide motif in Raver1 mediates splicing repression by interaction with the PTB RRM2 domain

Nat Struct Mol Biol. 2006 Sep;13(9):839-48. doi: 10.1038/nsmb1137. Epub 2006 Aug 27.


Polypyrimidine tract-binding protein (PTB) is a regulatory splicing repressor. Raver1 acts as a PTB corepressor for splicing of alpha-tropomyosin (Tpm1) exon 3. Here we define a minimal region of Raver1 that acts as a repressor domain when recruited to RNA. A conserved [S/G][I/L]LGxxP motif is essential for splicing repressor activity and sufficient for interaction with PTB. An adjacent proline-rich region is also essential for repressor activity but not for PTB interaction. NMR analysis shows that LLGxxP peptides interact with a hydrophobic groove on the dorsal surface of the RRM2 domain of PTB, which constitutes part of the minimal repressor region of PTB. The requirement for the PTB-Raver1 interaction that we have characterized may serve to bring the additional repressor regions of both proteins into a configuration that allows them to synergistically effect exon skipping.

Publication types

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

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Carrier Proteins / chemistry*
  • Carrier Proteins / metabolism*
  • Fluorescence Resonance Energy Transfer
  • HeLa Cells
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation / genetics
  • Nuclear Proteins / chemistry*
  • Nuclear Proteins / metabolism*
  • Polypyrimidine Tract-Binding Protein / chemistry*
  • Polypyrimidine Tract-Binding Protein / metabolism*
  • Proline / metabolism
  • Protein Binding
  • Protein Structure, Tertiary
  • RNA / genetics
  • RNA / metabolism
  • RNA Splicing / genetics*
  • Recombinant Fusion Proteins / metabolism


  • Carrier Proteins
  • Nuclear Proteins
  • Recombinant Fusion Proteins
  • Polypyrimidine Tract-Binding Protein
  • RNA
  • Proline