title: The effect of U1 snRNA binding free energy on the selection of 5' splice sites.
abstract: The importance of U1 snRNA binding free energy in the regulation of alternative splicing has been studied in some genes with site-directed mutagenesis. Here we report a large-scale analysis of its impact on 5' splice site (5'ss) selection in human genome. The results show that free energy exerts different effects on alternative 5'ss choice in different situations and -8.1 kcal/mol is a threshold. When both free energies of two competing 5'ss are larger than -8.1 kcal/mol, the 5'ss with lower free energy is more frequently used. However, in other pairs of 5'ss, lower-free-energy 5'ss does not seem to be favored and even the other 5'ss is used more frequently, which suggests that very low binding free energy would impair splicing. Some observations hold true only for those alternative 5' splicing with short alternative exons (<50nt), which implies a complex mechanism of 5'ss selection involving both U1 snRNA binding free energy and regulatory factors.
authors.affiliation: MOE Key Laboratory of Bioinformatics, Department of Automation, Tsinghua University, Beijing, China.
authors.forename: Jianning
authors.initials: J
authors.lastname: Bi
authors.forename: Huiyu
authors.initials: H
authors.lastname: Xia
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.forename: Xuegong
authors.initials: X
authors.lastname: Zhang
authors.forename: Yanda
authors.initials: Y
authors.lastname: Li
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D001665:Binding Sites; D003198:Computer Simulation; D004735:Energy Transfer; D008956:Models, Chemical; D008957:Models, Genetic; D008958:Models, Molecular; D015233:Models, Statistical; D022821:RNA Splice Sites / Q000235:genetics*; D012342:RNA, Small Nuclear / Q000737:chemistry* / Q000235:genetics*; D017423:Sequence Analysis, RNA / Q000379:methods*; D013329:Structure-Activity Relationship
chemical_list: D022821:RNA Splice Sites; D012342:RNA, Small Nuclear; C405483:U1 small nuclear RNA