TCAB1 prevents nucleolar accumulation of the telomerase RNA to facilitate telomerase assembly.
TCAB1 prevents nucleolar accumulation of the telomerase RNA to facilitate telomerase assembly.
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DOI：
10.1016/j.celrep.2023.112577
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发表时间：
2023-06-27
期刊：
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
各种RNA定位于非膜结合的细胞区室如核仁和卡哈尔体对其稳定性和功能至关重要。从这些相分离的细胞器中募集和排除RNA的分子机制还不完全清楚。端粒酶是一种核糖核蛋白，由端粒酶逆转录酶（TERT）、端粒酶RNA（TR）和几种辅助蛋白（包括TCAB1）组成。在这里，我们表明，在TCAB1的情况下，TR的大部分是紧密结合的核仁，而TERT在很大程度上被排除在核仁之外，减少端粒酶组装。这表明非膜结合核仁的核区室化抵消了端粒酶组装，并且TCAB1需要将TR保留在核质中。我们的工作提供了深入了解的机制和功能后果的RNA招聘相分离形成的细胞器，并证明TCAB1在端粒酶组装中起着重要的作用。Klump等人表明TCAB1，一种端粒酶辅因子，促进端粒酶组装。结果表明，TCAB1不是端粒酶催化所必需的，并且TCAB1与端粒酶RNA的结合阻止其进入核仁以促进其与端粒酶逆转录酶的相互作用。
Localization of a variety of RNAs to non-membrane-bound cellular compartments such as nucleoli and Cajal bodies is critical for their stability and function. The molecular mechanisms that underly the recruitment and exclusion of RNAs from these phase-separated organelles is incompletely understood. Telomerase is a ribonucleoprotein composed of the reverse transcriptase protein telomerase reverse transcriptase (TERT), the telomerase RNA (TR), and several auxiliary proteins, including TCAB1. Here we show that in the absence of TCAB1, a large fraction of TR is tightly bound to the nucleolus, while TERT is largely excluded from the nucleolus, reducing telomerase assembly. This suggests that nuclear compartmentalization by the non-membrane-bound nucleolus counteracts telomerase assembly, and TCAB1 is required to retain TR in the nucleoplasm. Our work provides insight into the mechanism and functional consequences of RNA recruitment to organelles formed by phase separation and demonstrates that TCAB1 plays an important role in telomerase assembly. Klump et al. show that TCAB1, a telomerase cofactor, facilitates telomerase assembly. The results indicate that TCAB1 is not required for telomerase catalysis and that TCAB1 association with the telomerase RNA prevents its entry into the nucleolus to facilitate its interaction with the telomerase reverse transcriptase.
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端粒蛋白TPP1的TEL斑块介导端粒酶募集和加工性。
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
7.7
作者：
Schmidt JC;Dalby AB;Cech TR
通讯作者：
Cech TR
DOI：
10.1038/nrg3246
发表时间：
2012-10
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
5.3
作者：
Egan, Emily D.;Collins, Kathleen
通讯作者：
Collins, Kathleen
影响因子：
3.5
作者：
Heiss, NS;Girod, A;Poustka, A
通讯作者：
Poustka, A