Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 107, Issue 9, Pages 4105-4110Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0907072107
Keywords
alternative splicing; polypyrimidine tract-binding protein; protein-RNA interactions
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Funding
- Swiss National Science Foundation National Center
- European Alternative Splicing Network
- National Institutes of Health [GM085116]
- National Science Foundation [MCB0747285]
- Div Of Molecular and Cellular Bioscience
- Direct For Biological Sciences [0747285] Funding Source: National Science Foundation
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Alternative splicing plays an important role in generating proteome diversity. The polypyrimidine tract-binding protein (PTB) is a key alternative splicing factor involved in exon repression. It has been proposed that PTB acts by looping out exons flanked by pyrimidine tracts. We present fluorescence, NMR, and in vivo splicing data in support of a role of PTB in inducing RNA loops. We show that the RNA recognition motifs (RRMs) 3 and 4 of PTB can bind two distant pyrimidine tracts and bring their 5' and 3' ends in close proximity, thus looping the RNA. Efficient looping requires an intervening sequence of 15 nucleotides or longer between the pyrimidine tracts. RRM3 and RRM4 bind the 5' and the 3' pyrimidine tracts, respectively, in a specific directionality and work synergistically for efficient splicing repression in vivo.
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