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调控人类端粒酶 RNA 的生物发生和定位。

Regulation of human telomerase RNA biogenesis and localization.

机构信息

Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada.

Jewish General Hospital, Lady Davis Institute, Montreal, Quebec, Canada.

出版信息

RNA Biol. 2021 Mar;18(3):305-315. doi: 10.1080/15476286.2020.1809196. Epub 2020 Sep 2.

DOI:10.1080/15476286.2020.1809196
PMID:32813614
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7954027/
Abstract

Maintenance of telomeres is essential for genome integrity and replicative capacity in eukaryotic cells. Telomerase, the ribonucleoprotein complex that catalyses telomere synthesis is minimally composed of a reverse transcriptase and an RNA component. The sequence and structural domains of human telomerase RNA (hTR) have been extensively characterized, while the regulation of hTR transcription, maturation, and localization, is not fully understood. Here, we provide an up-to-date review of hTR, with an emphasis on current breakthroughs uncovering the mechanisms of hTR maturation and localization.

摘要

端粒的维持对于真核细胞的基因组完整性和复制能力至关重要。端粒酶是一种催化端粒合成的核蛋白复合物,其最小组成部分是逆转录酶和 RNA 成分。人类端粒酶 RNA(hTR)的序列和结构域已得到广泛描述,而 hTR 转录、成熟和定位的调控机制尚不完全清楚。本文重点介绍 hTR 成熟和定位机制方面的最新研究进展,对 hTR 进行了全面综述。

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Regulation of human telomerase RNA biogenesis and localization.调控人类端粒酶 RNA 的生物发生和定位。
RNA Biol. 2021 Mar;18(3):305-315. doi: 10.1080/15476286.2020.1809196. Epub 2020 Sep 2.
2
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Human telomerase reverse transcriptase binds to a pre-organized hTR in vivo exposing its template.人类端粒酶逆转录酶在体内与预先组装好的人端粒酶RNA结合,从而暴露其模板。
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本文引用的文献

1
Single-Molecule Imaging of Telomerase RNA Reveals a Recruitment-Retention Model for Telomere Elongation.单分子成像揭示端粒酶 RNA 募集-保留模型用于端粒延长。
Mol Cell. 2020 Jul 2;79(1):115-126.e6. doi: 10.1016/j.molcel.2020.05.005. Epub 2020 Jun 3.
2
Small-Molecule PAPD5 Inhibitors Restore Telomerase Activity in Patient Stem Cells.小分子PAPD5抑制剂可恢复患者干细胞中的端粒酶活性。
Cell Stem Cell. 2020 Jun 4;26(6):896-909.e8. doi: 10.1016/j.stem.2020.03.016. Epub 2020 Apr 21.
3
Regulation of human telomerase in homeostasis and disease.人类端粒酶在体内平衡和疾病中的调控。
Nat Rev Mol Cell Biol. 2020 Jul;21(7):384-397. doi: 10.1038/s41580-020-0234-z. Epub 2020 Apr 2.
4
A Two-Layered Targeting Mechanism Underlies Nuclear RNA Sorting by the Human Exosome.双层靶向机制是人类核外切体进行核 RNA 分拣的基础。
Cell Rep. 2020 Feb 18;30(7):2387-2401.e5. doi: 10.1016/j.celrep.2020.01.068.
5
Loss of Human TGS1 Hypermethylase Promotes Increased Telomerase RNA and Telomere Elongation.人类 TGS1 超甲基化酶缺失促进端粒酶 RNA 和端粒延长。
Cell Rep. 2020 Feb 4;30(5):1358-1372.e5. doi: 10.1016/j.celrep.2020.01.004.
6
HnRNP F/H associate with hTERC and telomerase holoenzyme to modulate telomerase function and promote cell proliferation.hnRNP F/H 与 hTERC 和端粒酶全酶结合,调节端粒酶功能并促进细胞增殖。
Cell Death Differ. 2020 Jun;27(6):1998-2013. doi: 10.1038/s41418-019-0483-6. Epub 2019 Dec 20.
7
The Nuclear RNA Exosome and Its Cofactors.核 RNA 外切体及其辅助因子。
Adv Exp Med Biol. 2019;1203:113-132. doi: 10.1007/978-3-030-31434-7_4.
8
Nopp140-mediated concentration of telomerase in Cajal bodies regulates telomere length.Nopp140 介导的端粒酶在 Cajal 体中的集中调节端粒长度。
Mol Biol Cell. 2019 Dec 15;30(26):3136-3150. doi: 10.1091/mbc.E19-08-0429. Epub 2019 Oct 30.
9
, the nuclear exosome targeting component, is mutated in familial pulmonary fibrosis and is required for telomerase RNA maturation.核 exosome 靶向组件在家族性肺纤维化中发生突变,并且是端粒酶 RNA 成熟所必需的。
Genes Dev. 2019 Oct 1;33(19-20):1381-1396. doi: 10.1101/gad.326785.119. Epub 2019 Sep 5.
10
SMUG1 Promotes Telomere Maintenance through Telomerase RNA Processing.SMUG1 通过端粒酶 RNA 加工促进端粒维持。
Cell Rep. 2019 Aug 13;28(7):1690-1702.e10. doi: 10.1016/j.celrep.2019.07.040.