Lareau Liana F, Brenner Steven E
Departments of Molecular and Cell Biology and Plant and Microbial Biology, University of California, Berkeley Department of Biochemistry, Stanford University School of Medicine.
Departments of Molecular and Cell Biology and Plant and Microbial Biology, University of California, Berkeley
Mol Biol Evol. 2015 Apr;32(4):1072-9. doi: 10.1093/molbev/msv002. Epub 2015 Jan 8.
Ultraconserved elements, unusually long regions of perfect sequence identity, are found in genes encoding numerous RNA-binding proteins including arginine-serine rich (SR) splicing factors. Expression of these genes is regulated via alternative splicing of the ultraconserved regions to yield mRNAs that are degraded by nonsense-mediated mRNA decay (NMD), a process termed unproductive splicing (Lareau et al. 2007; Ni et al. 2007). As all human SR genes are affected by alternative splicing and NMD, one might expect this regulation to have originated in an early SR gene and persisted as duplications expanded the SR family. But in fact, unproductive splicing of most human SR genes arose independently (Lareau et al. 2007). This paradox led us to investigate the origin and proliferation of unproductive splicing in SR genes. We demonstrate that unproductive splicing of the splicing factor SRSF5 (SRp40) is conserved among all animals and even observed in fungi; this is a rare example of alternative splicing conserved between kingdoms, yet its effect is to trigger mRNA degradation. As the gene duplicated, the ancient unproductive splicing was lost in paralogs, and distinct unproductive splicing evolved rapidly and repeatedly to take its place. SR genes have consistently employed unproductive splicing, and while it is exceptionally conserved in some of these genes, turnover in specific events among paralogs shows flexible means to the same regulatory end.
超保守元件是指具有完美序列同一性的异常长区域，在编码包括富含精氨酸 - 丝氨酸（SR）剪接因子在内的众多RNA结合蛋白的基因中被发现。这些基因的表达通过超保守区域的可变剪接来调控，从而产生会被无义介导的mRNA降解（NMD）所降解的mRNA，这一过程被称为无效剪接（拉罗等人，2007年；倪等人，2007年）。由于所有人类SR基因都受到可变剪接和NMD的影响，人们可能会认为这种调控起源于早期的SR基因，并随着基因复制使SR家族扩大而持续存在。但事实上，大多数人类SR基因的无效剪接是独立产生的（拉罗等人，2007年）。这一矛盾促使我们去研究SR基因中无效剪接的起源和扩散。我们证明，剪接因子SRSF5（SRp40）的无效剪接在所有动物中都是保守的，甚至在真菌中也能观察到；这是一个在不同界之间保守的可变剪接的罕见例子，但其作用是触发mRNA降解。随着基因复制，古老的无效剪接在旁系同源基因中丢失，不同的无效剪接迅速且反复地进化以取而代之。SR基因一直采用无效剪接，虽然在其中一些基因中它异常保守，但旁系同源基因中特定事件的更替显示出实现相同调控目的的灵活方式。
