USP15通过去泛素化PRP31来调节剪接体的动态蛋白质-蛋白质相互作用。
USP15 regulates dynamic protein-protein interactions of the spliceosome through deubiquitination of PRP31.
作者信息
Das Tanuza, Park Joon Kyu, Park Jinyoung, Kim Eunji, Rape Michael, Kim Eunice EunKyeong, Song Eun Joo
机构信息
Molecular Recognition Research Center, Korea Institute of Science and Technology, Hwarangno 14-gil 5, Seongbuk-gu, Seoul 02792, Korea.
Biomedical Research Institute, Korea Institute of Science and Technology, Hwarangno 14-gil 5, Seongbuk-gu 02792, Seoul, Korea.
出版信息
Nucleic Acids Res. 2017 May 5;45(8):4866-4880. doi: 10.1093/nar/gkw1365.
Post-translational modifications contribute to the spliceosome dynamics by facilitating the physical rearrangements of the spliceosome. Here, we report USP15, a deubiquitinating enzyme, as a regulator of protein-protein interactions for the spliceosome dynamics. We show that PRP31, a component of U4 snRNP, is modified with K63-linked ubiquitin chains by the PRP19 complex and deubiquitinated by USP15 and its substrate targeting factor SART3. USP15SART3 makes a complex with USP4 and this ternary complex serves as a platform to deubiquitinate PRP31 and PRP3. The ubiquitination and deubiquitination status of PRP31 regulates its interaction with the U5 snRNP component PRP8, which is required for the efficient splicing of chromosome segregation related genes, probably by stabilizing the U4/U6.U5 tri-snRNP complex. Collectively, our data suggest that USP15 plays a key role in the regulation of dynamic protein-protein interactions of the spliceosome.
翻译后修饰通过促进剪接体的物理重排来影响剪接体动力学。在此，我们报道去泛素化酶USP15作为剪接体动力学中蛋白质-蛋白质相互作用的调节因子。我们发现，U4 snRNP的一个组分PRP31被PRP19复合体修饰为K63连接的泛素链，并被USP15及其底物靶向因子SART3去泛素化。USP15-SART3与USP4形成复合体，这个三元复合体作为去泛素化PRP31和PRP3的平台。PRP31的泛素化和去泛素化状态调节其与U5 snRNP组分PRP8的相互作用，这可能通过稳定U4/U6·U5三snRNP复合体来实现，而这对于染色体分离相关基因的有效剪接是必需的。总体而言，我们的数据表明USP15在剪接体动态蛋白质-蛋白质相互作用的调节中起关键作用。
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