When SUMO met splicing

Spliceosomal proteins have been revealed as SUMO conjugation targets. Moreover, we have reported that many of these are in a SUMO-conjugated form when bound to a pre-mRNA substrate during a splicing reaction. We demonstrated that SUMOylation of Prp3 (PRPF3), a component of the U4/U6 di-snRNP, is required for U4/U6•U5 tri-snRNP formation and/or recruitment to active spliceosomes. Expanding upon our previous results, we have shown that the splicing factor SRSF1 stimulates SUMO conjugation to several spliceosomal proteins. Given the relevance of the splicing process, as well as the complex and dynamic nature of its governing machinery, the spliceosome, the molecular mechanisms that modulate its function represent an attractive topic of research. We posit that SUMO conjugation could represent a way of modulating spliceosome assembly and thus, splicing efficiency. How cycles of SUMOylation/de-SUMOylation of spliceosomal proteins become integrated throughout the highly choreographed spliceosomal cycle awaits further investigation.

剪接体蛋白已被证实为SUMO偶联修饰的靶标。此外，本团队此前已报道，在剪接反应过程中，这类蛋白中诸多成员与前体mRNA（pre-mRNA）底物结合时，即处于SUMO偶联修饰状态。本研究证实，U4/U6二聚小核核糖核蛋白颗粒（U4/U6 di-snRNP）的组成成分Prp3（PRPF3）的SUMO化修饰，是U4/U6•U5三聚小核核糖核蛋白颗粒（U4/U6•U5 tri-snRNP）组装，以及/或是招募至活性剪接体所必需的过程。在前期研究基础上，本团队进一步证实，剪接因子SRSF1可促进多种剪接体蛋白的SUMO偶联修饰。鉴于剪接过程的重要性，以及其调控机器——剪接体所具备的复杂且动态的特性，调控剪接体功能的分子机制是极具吸引力的研究课题。本研究推测，SUMO偶联修饰或可作为调控剪接体组装、进而影响剪接效率的一种途径。剪接体蛋白的SUMO化/去SUMO化循环如何整合进高度精密调控的剪接体循环过程，这一问题尚待进一步研究。