A nuclear protein quality control system for elimination of nucleolus-related inclusions.

IF 9.4 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY EMBO Journal Pub Date : 2025-02-01 Epub Date: 2024-12-17 DOI:10.1038/s44318-024-00333-9
Lorène Brunello, Jolanta Polanowska, Léo Le Tareau, Chantal Maghames, Virginie Georget, Charlotte Guette, Karima Chaoui, Stéphanie Balor, Marie-Françoise O'Donohue, Marie-Pierre Bousquet, Pierre-Emmanuel Gleizes, Dimitris P Xirodimas
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Abstract

The identification of pathways that control elimination of protein inclusions is essential to understand the cellular response to proteotoxicity, particularly in the nuclear compartment, for which our knowledge is limited. We report that stress-induced nuclear inclusions related to the nucleolus are eliminated upon stress alleviation during the recovery period. This process is independent of autophagy/lysosome and CRM1-mediated nuclear export pathways, but strictly depends on the ubiquitin-activating E1 enzyme, UBA1, and on nuclear proteasomes that are recruited into the formed inclusions. UBA1 activity is essential only for the recovery process but dispensable for nuclear inclusion formation. Furthermore, the E3 ligase HUWE1 and HSP70 are components of the ubiquitin/chaperone systems that promote inclusion elimination. The recovery process also requires RNA Pol I-dependent production of the lncRNA IGS42 during stress. IGS42 localises within the formed inclusions and promotes their elimination by preserving the mobility of resident proteins. These findings reveal a protein quality control system that operates within the nucleus for the elimination of stress-induced nucleolus-related inclusions.

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消除核仁相关内含物的核蛋白质量控制系统。
识别控制蛋白包涵体消除的途径对于理解细胞对蛋白质毒性的反应至关重要,特别是在核室中,对此我们的知识有限。我们报道应力诱导的核仁核包裹体在恢复期间应力缓解后被消除。该过程独立于自噬/溶酶体和crm1介导的核输出途径,但严格依赖于泛素激活E1酶UBA1和被招募到形成的内含体中的核蛋白酶体。UBA1活性仅对恢复过程至关重要,但对核包裹体的形成是必不可少的。此外,E3连接酶HUWE1和HSP70是促进内含物消除的泛素/伴侣系统的组成部分。在应激过程中,恢复过程也需要依赖RNA Pol i的lncRNA IGS42的产生。IGS42定位于形成的包涵体内,并通过保持驻留蛋白的移动性来促进其消除。这些发现揭示了一种在细胞核内运作的蛋白质质量控制系统,用于消除应力诱导的核仁相关内含物。
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来源期刊
EMBO Journal
EMBO Journal 生物-生化与分子生物学
CiteScore
18.90
自引率
0.90%
发文量
246
审稿时长
1.5 months
期刊介绍: The EMBO Journal has stood as EMBO's flagship publication since its inception in 1982. Renowned for its international reputation in quality and originality, the journal spans all facets of molecular biology. It serves as a platform for papers elucidating original research of broad general interest in molecular and cell biology, with a distinct focus on molecular mechanisms and physiological relevance. With a commitment to promoting articles reporting novel findings of broad biological significance, The EMBO Journal stands as a key contributor to advancing the field of molecular biology.
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