Bi Jianning, Xia Huiyu, Li Fei, Zhang Xuegong, Li Yanda
MOE Key Laboratory of Bioinformatics, Department of Automation, Tsinghua University, Beijing, China.
Biochem Biophys Res Commun. 2005 Jul 22;333(1):64-9. doi: 10.1016/j.bbrc.2005.05.078.
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.
通过定点诱变，在一些基因中研究了U1 snRNA结合自由能在可变剪接调控中的重要性。在此，我们报告了对其在人类基因组中对5'剪接位点（5'ss）选择影响的大规模分析。结果表明，自由能在不同情况下对可变5'ss选择有不同影响，且-8.1千卡/摩尔是一个阈值。当两个相互竞争的5'ss的自由能均大于-8.1千卡/摩尔时，自由能较低的5'ss更常被使用。然而，在其他5'ss对中，自由能较低的5'ss似乎并不占优势，甚至另一个5'ss更常被使用，这表明极低的结合自由能会损害剪接。一些观察结果仅适用于那些具有短可变外显子（<50nt）的可变5'剪接，这意味着5'ss选择的机制复杂，涉及U1 snRNA结合自由能和调控因子。
