The ubiquitin-specific protease USP36 SUMOylates EXOSC10 and promotes the nucleolar RNA exosome function in rRNA processing.
The ubiquitin-specific protease USP36 SUMOylates EXOSC10 and promotes the nucleolar RNA exosome function in rRNA processing.
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DOI：
10.1093/nar/gkad140
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发表时间：
2023-05-08
影响因子：
14.9
通讯作者：
中科院分区：
文献类型：
--
作者：
RNA外泌体是一种重要的3′至5′核糖核酸外切酶复合物，介导几乎所有真核生物RNA的降解、加工和质量控制。核仁RNA外泌体由一个9亚基核心和一个分布在3′至5′端的核酸外切酶EXOSC 10组成，在加工和降解包括前体rRNA在内的核仁RNA中起着关键作用。然而，RNA外泌体在核仁中是如何被调控的还知之甚少。在这里，我们报告说，核仁泛素特异性蛋白酶USP 36是一种新的调节核仁RNA外泌体。USP 36通过与核仁中的EXOSC 10直接相互作用与RNA外泌体结合。有趣的是，USP 36并不显著调节EXOSC 10和其他测试的外泌体亚基的水平。相反，它介导在赖氨酸（K）583处的EXOSC 10 SUMO化。突变K583削弱了EXOSC 10与pre-rRNA的结合，K583 R突变体未能挽救内源性EXOSC 10敲低引起的rRNA加工缺陷和细胞生长抑制。此外，EXOSC 10 SUMO化在细胞中响应于核糖体生物发生的扰动而显著减少。总之，这些结果表明，USP 36作为SUMO连接酶促进EXOSC 10 SUMO化，这对核糖体生物发生中的RNA外泌体功能至关重要。
The RNA exosome is an essential 3′ to 5′ exoribonuclease complex that mediates degradation, processing and quality control of virtually all eukaryotic RNAs. The nucleolar RNA exosome, consisting of a nine-subunit core and a distributive 3′ to 5′ exonuclease EXOSC10, plays a critical role in processing and degrading nucleolar RNAs, including pre-rRNA. However, how the RNA exosome is regulated in the nucleolus is poorly understood. Here, we report that the nucleolar ubiquitin-specific protease USP36 is a novel regulator of the nucleolar RNA exosome. USP36 binds to the RNA exosome through direct interaction with EXOSC10 in the nucleolus. Interestingly, USP36 does not significantly regulate the levels of EXOSC10 and other tested exosome subunits. Instead, it mediates EXOSC10 SUMOylation at lysine (K) 583. Mutating K583 impaired the binding of EXOSC10 to pre-rRNAs, and the K583R mutant failed to rescue the defects in rRNA processing and cell growth inhibition caused by knockdown of endogenous EXOSC10. Furthermore, EXOSC10 SUMOylation is markedly reduced in cells in response to perturbation of ribosomal biogenesis. Together, these results suggest that USP36 acts as a SUMO ligase to promote EXOSC10 SUMOylation critical for the RNA exosome function in ribosome biogenesis.
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影响因子：
11.8
作者：
Cubenas-Potts, Caelin;Matunis, Michael J.
通讯作者：
Matunis, Michael J.
影响因子：
3.3
作者：
Castle CD;Cassimere EK;Denicourt C
通讯作者：
Denicourt C
影响因子：
64.5
作者：
Halbach, Felix;Reichelt, Peter;Conti, Elena
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Conti, Elena
影响因子：
16.6
作者：
Hendriks, Ivo A.;D'Souza, Rochelle C.;Chang, Jer-Gung;Mann, Matthias;Vertegaal, Alfred C. O.
通讯作者：
Vertegaal, Alfred C. O.
影响因子：
5.3
作者：
Dai, MS;Zeng, SX;Lu, H
通讯作者：
Lu, H