Regulation of splicing enhancer activities by RNA secondary structures

Wei Liu 1 Yu Zhou 1, 2, 3 Zexi Hu 1 Tao Sun 1 Alain Denise 2, 4, 5 Xiang-Dong Fu 1, 3 Yi Zhang 1, 6
5 AMIB - Algorithms and Models for Integrative Biology
LIX - Laboratoire d'informatique de l'École polytechnique [Palaiseau], LRI - Laboratoire de Recherche en Informatique, UP11 - Université Paris-Sud - Paris 11, Inria Saclay - Ile de France
Abstract : 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.
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Submitted on : Tuesday, November 9, 2010 - 2:15:00 PM
Last modification on : Wednesday, March 27, 2019 - 4:41:29 PM

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Wei Liu, Yu Zhou, Zexi Hu, Tao Sun, Alain Denise, et al.. Regulation of splicing enhancer activities by RNA secondary structures. FEBS Letters, Wiley, 2010, 584 (21), pp.4401-7. ⟨10.1016/j.febslet.2010.09.039⟩. ⟨hal-00534366⟩

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