Journal
EMBO JOURNAL
Volume 29, Issue 4, Pages 749-760Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/emboj.2009.397
Keywords
RNA structure; SF2/ASF; spliceosome; U1snRNP; U2snRNP
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Funding
- Telethon Onlus Foundation (Italy) [GGP06147]
- European community [EURASNET-LSHG-CT-2005-518238]
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Abundance of pseudo splice sites in introns can potentially give rise to innumerable pseudoexons, outnumbering the real ones. Nonetheless, these are efficiently ignored by the splicing machinery, a process yet to be understood completely. Although numerous 50 splice site-like sequences functioning as splicing silencers have been found to be enriched in predicted human pseudoexons, the lack of active pseudoexons pose a fundamental challenge to how these U1snRNP-binding sites function in splicing inhibition. Here, we address this issue by focusing on a previously described pathological ATM pseudoexon whose inhibition is mediated by U1snRNP binding at intronic splicing processing element (ISPE), composed of a consensus donor splice site. Spliceosomal complex assembly demonstrates inefficient A complex formation when ISPE is intact, implying U1snRNP-mediated unproductive U2snRNP recruitment. Furthermore, interaction of SF2/ASF with its motif seems to be dependent on RNA structure and U1snRNP interaction. Our results suggest a complex combinatorial interplay of RNA structure and trans-acting factors in determining the splicing outcome and contribute to understanding the intronic splicing code for the ATM pseudoexon. The EMBO Journal (2010) 29, 749-760. doi: 10.1038/emboj.2009.397; Published online 21 January 2010
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