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The Ubiquitin-Specific Protease USP36 Promotes Small Nucleolar Ribonucleoprotein Group SUMOylation and is Essential for Ribosome Biogenesis

ABSTRACT: SUMOylation plays a crucial role in regulating diverse cellular processes including ribosome biogenesis. Proteomic analyses and experimental evidence showed that a number of nucleolar proteins involved in ribosome biogenesis are modified by SUMO. However, how these proteins are SUMOylated is less understood. Here, we report that USP36, a nucleolar deubiquitinating enzyme (DUB), promotes nucleolar SUMOylation. Overexpression of USP36 enhances nucleolar SUMOylation, whereas its knockdown or genetic deletion reduces the levels of SUMOylation. USP36 interacts with SUMO2 and Ubc9 and directly mediates SUMOylation in cells and in vitro. We show that USP36 promotes the SUMOylation of the small nucleolar ribonucleoprotein (snoRNP) components Nop58 and Nhp2 in cells and in vitro and their binding to snoRNAs. It also promotes the SUMOylation of snoRNP components Nop56 and DKC1. Functionally, we show that knockdown of USP36 markedly impairs rRNA processing and translation. Thus, USP36 promotes snoRNP group SUMOylation and is critical for ribosome biogenesis and protein translation.

INSTRUMENT(S): LTQ

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Phillip Wilmarth

LAB HEAD: Mu-Shui Dai

PROVIDER: PXD022987 | Pride | 2021-03-29

REPOSITORIES: pride

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			Action	DRS
	DAI1477_Control_1_35ul_75um_240min_20140327_VE2.ms2.gz	Other
	DAI1477_Control_1_35ul_75um_240min_20140327_VE2.raw	Raw
	DAI1477_Control_1_35ul_75um_240min_20140327_VE2.sqt.gz	Other
	DAI1477_Control_1_35ul_75um_240min_20140327_VE2.txt.gz	Txt
	DAI1477_USPS6_1_35ul_75um_240min_20140327_VE2.ms2.gz	Other

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The Ubiquitin-Specific Protease USP36 SUMOylates EXOSC10 and promotes the nucleolar RNA exosome function in rRNA processing

Project description:The RNA exosome is an essential 3’ to 5’ processing exoribonuclease complex that mediates degradation, processing, and quality control of virtually all eukaryotic RNAs. The nucleolar RNA exosome, consisting of a 9-subunit core and a distributive 3ʹ to 5ʹ exonuclease EXOSC10, plays a critical role in processing and degrading nucleolar RNAs, including pre-ribosomal RNA (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. Interestingly, USP36 does not significantly regulate the levels of EXOSC10 and other exosome subunits. Instead, it mediates EXOSC10 SUMOylation at Lys (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, indicating that EXOSC10 SUMOylation is critical for the exosome function in rRNA processing. Furthermore, USP36 itself is a rRNA-binding protein that associates pre-rRNA. These results suggest that USP36 acts as a novel SUMO ligase to mediate EXOSC10 SUMOylation critical for the RNA exosome function in rRNA processing and ribosome biogenesis.

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USP36 stabilizes nucleolar Snail1 to promote ribosome biogenesis and cancer cell survival upon ribotoxic stress

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