U1 snRNA Directly Interacts with Polypyrimidine Tract-Binding Protein during Splicing Repression

Shalini Sharma, Christophe Maris, Frédéric H.T. Allain, Douglas L. Black

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

Splicing of the c-src N1 exon is repressed by the polypyrimidine tract-binding protein (PTB or PTBP1). During exon repression, the U1 snRNP binds properly to the N1 exon 5' splice site but is made inactive by the presence of PTB. Examining the patterns of nuclease protection at this 5' splice site, we find that the interaction of U1 is altered by the adjacent PTB. Interestingly, UV crosslinking identifies a direct contact between the pre-mRNA-bound PTB and the U1 snRNA. EMSA, ITC, and NMR studies show that PTB RRMs 1 and 2 bind the pyrimidine-rich internal loop of U1 snRNA stem loop 4. The PTB/U1 interaction prevents further assembly of the U1 snRNP with spliceosomal components downstream. This precise interaction between a splicing regulator and an snRNA component of the spliceosome points to a range of different mechanisms for splicing regulation.

Original languageEnglish (US)
Pages (from-to)579-588
Number of pages10
JournalMolecular cell
Volume41
Issue number5
DOIs
StatePublished - Mar 4 2011
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'U1 snRNA Directly Interacts with Polypyrimidine Tract-Binding Protein during Splicing Repression'. Together they form a unique fingerprint.

  • Cite this