Polypyrimidine tract binding protein inhibits IgM pre-mRNA splicing by diverting U2 snRNA base-pairing away from the branch point
- Xuexiu Zheng1,
- Sunghee Cho1,
- Heegyum Moon1,
- Tiing Jen Loh1,
- Huyn Kyung Oh1,
- Michael R. Green2 and
- Haihong Shen1,3
- 1Department of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Korea
- 2Howard Hughes Medical Institute and Programs in Gene Function and Expression and Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
Abstract
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.
Keywords
- branch point
- pre-mRNA splicing
- polypyrimidine tract binding protein
- PTB
- splicing inhibitory complex
- U2 snRNA
Footnotes
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↵3 Corresponding author
E-mail haihongshen{at}gist.ac.kr
- Received December 2, 2013.
- Accepted January 27, 2014.
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