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Regulation of splicing enhancer activities by RNA secondary structures
Author(s) -
Liu Wei,
Zhou Yu,
Hu Zexi,
Sun Tao,
Denise Alain,
Fu Xiang-Dong,
Zhang Yi
Publication year - 2010
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2010.09.039
Subject(s) - minigene , enhancer , rna splicing , rna , nucleic acid secondary structure , biology , ribonucleoprotein , computational biology , exonic splicing enhancer , genetics , microbiology and biotechnology , gene , gene expression
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.