Journal
RNA
Volume 20, Issue 4, Pages 440-446Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1261/rna.043737.113
Keywords
branch point; pre-mRNA splicing; polypyrimidine tract binding protein; PTB; splicing inhibitory complex; U2 snRNA
Categories
Funding
- National Research Foundation (NRF) [NRF-2011-0016757, NRF-2013R 1A1A2062582, NRF-2013R1A1A2061321]
- Ministry of Education, Science, and Technology (MEST), Republic of Korea
- Gwangju Institute of Science and Technology GIST
- National Institutes of Health [R01GM035490]
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The mouse immunoglobulin (IgM) pre-mRNA contains a splicing inhibitor that bears multiple binding sites for the splicing repressor polypyrimidine tract binding protein (PTB). Here we show that the inhibitor directs assembly of an ATP-dependent complex that contains PTB and U1 and U2 small nuclear RNAs (snRNAs). Unexpectedly, although U2 snRNA is present in the inhibitor complex, it is not base-paired to the branch point. We present evidence that inhibitor-bound PTB contacts U2 snRNA to promote base-pairing to an adjacent branch point-like sequence within the inhibitor, thereby preventing the U2 snRNA-branch point interaction and resulting in splicing repression. Our studies reveal a novel mechanism by which PTB represses splicing.
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