细胞中端粒酶 RNA 折叠的质量控制机制。

Quality-Control Mechanism for Telomerase RNA Folding in the Cell.

机构信息

Department of Biological Chemistry, School of Medicine, University of California, Irvine, CA 92697-1700, USA.

Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, CA 92697-4560, USA.

出版信息

Cell Rep. 2020 Dec 29;33(13):108568. doi: 10.1016/j.celrep.2020.108568.

DOI:10.1016/j.celrep.2020.108568

PMID:33378677

Abstract

Long non-coding RNAs can often fold into different conformations. Telomerase RNA, an essential component of the telomerase ribonucleoprotein (RNP) enzyme, must fold into a defined structure to fulfill its function with the protein catalytic subunit (TERT) and other accessory factors. However, the mechanism by which the correct folding of telomerase RNA is warranted in a cell is still unknown. Here we show that La-related protein Pof8 specifically recognizes the conserved pseudoknot region of telomerase RNA and instructs the binding of the Lsm2-8 complex to its mature 3' end, thus selectively protecting the correctly folded RNA from exonucleolytic degradation. In the absence of Pof8, TERT assembles with misfolded RNA and produces little telomerase activity. Therefore, Pof8 plays a key role in telomerase RNA folding quality control, ensuring that TERT only assembles with functional telomerase RNA to form active telomerase. Our finding reveals a mechanism for non-coding RNA folding quality control.

摘要

长非编码 RNA 通常可以折叠成不同的构象。端粒酶 RNA 是端粒酶核糖核蛋白（RNP）酶的必需组成部分，必须折叠成特定的结构，才能与蛋白质催化亚基（TERT）和其他辅助因子发挥其功能。然而，端粒酶 RNA 正确折叠在细胞中是如何得到保证的机制仍不清楚。在这里，我们表明 La 相关蛋白 Pof8 特异性识别端粒酶 RNA 的保守假结区域，并指导 Lsm2-8 复合物与其成熟 3'端结合，从而选择性地保护正确折叠的 RNA 免受核酸外切酶的降解。在没有 Pof8 的情况下，TERT 与错误折叠的 RNA 组装，产生的端粒酶活性很少。因此，Pof8 在端粒酶 RNA 折叠质量控制中发挥着关键作用，确保 TERT 仅与功能性端粒酶 RNA 组装形成具有活性的端粒酶。我们的发现揭示了一种非编码 RNA 折叠质量控制的机制。