TCAB1 防止端粒酶 RNA 在核仁中的积累，从而促进端粒酶的组装。

Suppr 超能文献

核心技术专利：CN118964589B侵权必究

Suppr 超能文献

核心技术专利：CN118964589B侵权必究

Institute for Quantitative Health Sciences and Engineering, Michigan State University, East Lansing, MI, USA; College of Osteopathic Medicine, Michigan State University, East Lansing, MI, USA; Cellular and Molecular Biology Graduate Program, College of Natural Sciences, Michigan State University, East Lansing, MI, USA.

Institute for Quantitative Health Sciences and Engineering, Michigan State University, East Lansing, MI, USA.

Cell Rep. 2023 Jun 27;42(6):112577. doi: 10.1016/j.celrep.2023.112577. Epub 2023 Jun 1.

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.

各种 RNA 定位于非膜结合的细胞区室，如核仁（nucleoli）和 Cajal 体（Cajal bodies），对于它们的稳定性和功能至关重要。然而，RNA 从这些相分离细胞器中招募和排除的分子机制还不完全清楚。端粒酶是一种由逆转录酶蛋白端粒酶逆转录酶（TERT）、端粒酶 RNA（TR）和几种辅助蛋白（包括 TCAB1）组成的核糖核蛋白。在这里，我们发现，在没有 TCAB1 的情况下，大量的 TR 与核仁紧密结合，而 TERT 则主要被排除在核仁之外，从而减少了端粒酶的组装。这表明非膜结合的核仁通过核区室化来对抗端粒酶的组装，并且 TCAB1 需要将 TR 保留在核质中。我们的工作为 RNA 被招募到相分离形成的细胞器的机制和功能后果提供了深入的了解，并表明 TCAB1 在端粒酶组装中发挥着重要作用。