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

Alexis P. Rideau, Clare Gooding, Peter J. Simpson, Tom P. Monie, Mike Lorenz, Stefan Hüttelmaier, Robert H. Singer, Stephen Matthews, Stephen Curry, Christopher W J Smith

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

Polypyrimidine tract-binding protein (PTB) is a regulatory splicing repressor. Raver1 acts as a PTB corepressor for splicing of α-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.

Original languageEnglish (US)
Pages (from-to)839-848
Number of pages10
JournalNature Structural and Molecular Biology
Volume13
Issue number9
DOIs
StatePublished - Sep 2006

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Polypyrimidine Tract-Binding Protein
Peptides
Exons
Protein Splicing
Co-Repressor Proteins
Tropomyosin
Protein Domains
Proline
RNA

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

Rideau, A. P., Gooding, C., Simpson, P. J., Monie, T. P., Lorenz, M., Hüttelmaier, S., ... Smith, C. W. J. (2006). A peptide motif in Raver1 mediates splicing repression by interaction with the PTB RRM2 domain. Nature Structural and Molecular Biology, 13(9), 839-848. https://doi.org/10.1038/nsmb1137

A peptide motif in Raver1 mediates splicing repression by interaction with the PTB RRM2 domain. / Rideau, Alexis P.; Gooding, Clare; Simpson, Peter J.; Monie, Tom P.; Lorenz, Mike; Hüttelmaier, Stefan; Singer, Robert H.; Matthews, Stephen; Curry, Stephen; Smith, Christopher W J.

In: Nature Structural and Molecular Biology, Vol. 13, No. 9, 09.2006, p. 839-848.

Research output: Contribution to journalArticle

Rideau, AP, Gooding, C, Simpson, PJ, Monie, TP, Lorenz, M, Hüttelmaier, S, Singer, RH, Matthews, S, Curry, S & Smith, CWJ 2006, 'A peptide motif in Raver1 mediates splicing repression by interaction with the PTB RRM2 domain', Nature Structural and Molecular Biology, vol. 13, no. 9, pp. 839-848. https://doi.org/10.1038/nsmb1137
Rideau, Alexis P. ; Gooding, Clare ; Simpson, Peter J. ; Monie, Tom P. ; Lorenz, Mike ; Hüttelmaier, Stefan ; Singer, Robert H. ; Matthews, Stephen ; Curry, Stephen ; Smith, Christopher W J. / A peptide motif in Raver1 mediates splicing repression by interaction with the PTB RRM2 domain. In: Nature Structural and Molecular Biology. 2006 ; Vol. 13, No. 9. pp. 839-848.
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