Position-dependent splicing activation and repression by SR and hnRNP proteins rely on common mechanisms
- Steffen Erkelenz1,3,
- William F. Mueller2,3,
- Melanie S. Evans2,
- Anke Busch2,
- Katrin Schöneweis1,
- Klemens J. Hertel2,4 and
- Heiner Schaal1,4
- 1Institute of Virology, Heinrich-Heine-University, D-40225 Düsseldorf, Germany
- 2Department of Microbiology and Molecular Genetics, University of California, Irvine, Irvine, California 92697-4025, USA
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↵3 These authors contributed equally to this work.
Abstract
Alternative splicing is regulated by splicing factors that modulate splice site selection. In some cases, however, splicing factors show antagonistic activities by either activating or repressing splicing. Here, we show that these opposing outcomes are based on their binding location relative to regulated 5′ splice sites. SR proteins enhance splicing only when they are recruited to the exon. However, they interfere with splicing by simply relocating them to the opposite intronic side of the splice site. hnRNP splicing factors display analogous opposing activities, but in a reversed position dependence. Activation by SR or hnRNP proteins increases splice site recognition at the earliest steps of exon definition, whereas splicing repression promotes the assembly of nonproductive complexes that arrest spliceosome assembly prior to splice site pairing. Thus, SR and hnRNP splicing factors exploit similar mechanisms to positively or negatively influence splice site selection.
Keywords
Footnotes
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↵4 Corresponding authors
E-mail khertel{at}uci.edu
E-mail schaal{at}uni-duesseldorf.de
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Article published online ahead of print. Article and publication date are at http://www.rnajournal.org/cgi/doi/10.1261/rna.037044.112.
- Received October 26, 2012.
- Accepted October 30, 2012.
- Copyright © 2013 RNA Society