Institut de recherches cliniques de Montréal, Montréal, Canada.
St-Patrick Research Group in Basic Oncology, Laval University Cancer Research Center, Axe Oncologie du Centre de Recherche du CHU de Québec-Université Laval, Québec City, Canada.
Elife. 2020 Nov 23;9:e61264. doi: 10.7554/eLife.61264.
Nuclear export of messenger RNAs (mRNAs) is intimately coupled to their synthesis. pre-mRNAs assemble into dynamic ribonucleoparticles as they are being transcribed, processed, and exported. The role of ubiquitylation in this process is increasingly recognized but, while a few E3 ligases have been shown to regulate nuclear export, evidence for deubiquitylases is currently lacking. Here we identified deubiquitylase Ubp15 as a regulator of nuclear export in Ubp15 interacts with both RNA polymerase II and the nuclear pore complex, and its deletion reverts the nuclear export defect of E3 ligase Rsp5 mutants. The deletion of leads to hyper-ubiquitylation of the main nuclear export receptor Mex67 and affects its association with THO, a complex coupling transcription to mRNA processing and involved in the recruitment of mRNA export factors to nascent transcripts. Collectively, our data support a role for Ubp15 in coupling transcription to mRNA export.
信使 RNA(mRNA)的核输出与它们的合成密切相关。前体 mRNA 在转录、加工和输出过程中组装成动态核糖核蛋白。泛素化在这个过程中的作用越来越受到重视,但尽管已经发现了一些 E3 连接酶来调节核输出,但目前还没有关于去泛素酶的证据。在这里,我们鉴定出去泛素酶 Ubp15 是核输出的调节剂,它与 RNA 聚合酶 II 和核孔复合物相互作用,其缺失逆转了 E3 连接酶 Rsp5 突变体的核输出缺陷。的缺失导致主要核输出受体 Mex67 的过度泛素化,并影响其与 THO 的结合,THO 是一个将转录与 mRNA 加工偶联的复合物,并参与将 mRNA 输出因子募集到新生转录本。总的来说,我们的数据支持 Ubp15 在将转录与 mRNA 输出偶联中的作用。