4.5 Article

Regulation of splicing enhancer activities by RNA secondary structures

Journal

FEBS LETTERS
Volume 584, Issue 21, Pages 4401-4407

Publisher

WILEY
DOI: 10.1016/j.febslet.2010.09.039

Keywords

Alternative splicing; Secondary structure; ESE

Funding

  1. China 863 program [2007AA02Z112]
  2. NSFC [30770422]
  3. China 973 program [2005CB724604]

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In this report, we studied the effect of RNA structures on the activity of exonic splicing enhancers on the SMN1 minigene model by engineering known ESEs into different positions of stable hairpins. We found that as short as 7-bp stem is sufficient to abolish the enhancer activity. When placing ESEs in the loop region, AG-rich ESEs are fully active, but a UCG-rich ESE is not because of additional structural constraints. ESEs placed adjacent to the 3' end of the hairpin structure display high enhancer activity, regardless of their sequence identities. These rules explain the suppression of multiple ESEs by point mutations that result in a stable RNA structure, and provide an additional mechanism for the C6T mutation in SMN2. (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

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