title: Regulation of splicing enhancer activities by RNA secondary structures.
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.
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.forename: Zexi
authors.initials: Z
authors.lastname: Hu
authors.forename: Tao
authors.initials: T
authors.lastname: Sun
authors.forename: Alain
authors.initials: A
authors.lastname: Denise
authors.forename: Xiang-Dong
authors.initials: XD
authors.lastname: Fu
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D020029:Base Pairing; D001483:Base Sequence; D005091:Exons / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D055029:Inverted Repeat Sequences; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry* / Q000235:genetics*; D012326:RNA Splicing / Q000235:genetics*; D020871:RNA Stability; D038621:Regulatory Sequences, Ribonucleic Acid / Q000235:genetics*; D055533:Survival of Motor Neuron 1 Protein / Q000235:genetics; D013696:Temperature
chemical_list: D038621:Regulatory Sequences, Ribonucleic Acid; D055533:Survival of Motor Neuron 1 Protein; D012313:RNA