TERRA 长非编码 RNA：处于端粒损伤、挽救和信号传递的中间阶段。

IF 6 2区生物学 Q1 CELL BIOLOGY

Current Opinion in Cell Biology Pub Date : 2024-09-28 DOI:10.1016/j.ceb.2024.102437

Eftychia Kyriacou, Joachim Lingner

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引用次数: 0

摘要

TERRA长非编码RNA在端粒的功能和维护中发挥着关键作用。它们可以协调端粒染色质重塑，通过端粒酶和同源定向修复来调节端粒的维持，并参与端粒DNA损伤反应。TERRA通过碱基配对与染色体末端结合形成R环，这是由RAD51 DNA重组酶及其伙伴RAD51AP1介导的。端粒 R 环干扰复制叉的进行，刺激端粒维护从半保守 DNA 复制转向同源定向修复（HDR）。后一种机制被缺乏端粒酶的癌细胞亚群（称为 ALT）所利用。此外，TERRA 还能在衰老过程中刺激短端粒的 HDR，延缓细胞衰老。在癌变过程中，当端粒被侵蚀的细胞进入复制危机时，TERRA作为一种信号分子介导自噬细胞死亡。

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TERRA long noncoding RNA: At the interphase of telomere damage, rescue and signaling

TERRA long noncoding RNAs play key roles in telomere function and maintenance. They can orchestrate telomeric chromatin remodeling, regulate telomere maintenance by telomerase and homology-directed repair, and they participate in the telomeric DNA damage response. TERRA associates with chromosome ends through base-pairing forming R-loops, which are mediated by the RAD51 DNA recombinase and its partner RAD51AP1. Telomeric R-loops interfere with replication fork progression, stimulating a switch of telomere maintenance from semiconservative DNA replication to homology-directed repair (HDR). The latter mechanism is exploited by a subset of cancer cells that lack telomerase, referred to as ALT. In addition, TERRA stimulates HDR at short telomeres during aging, delaying cellular senescence. During carcinogenesis, when cells with eroded telomeres enter replicative crisis, TERRA acts as a signaling molecule to mediate autophagic cell death.

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来源期刊

Current Opinion in Cell Biology 生物-细胞生物学

CiteScore

14.60

自引率

1.30%

发文量

审稿时长

93 days

期刊介绍： Current Opinion in Cell Biology (COCEBI) is a highly respected journal that specializes in publishing authoritative, comprehensive, and systematic reviews in the field of cell biology. The journal's primary aim is to provide a clear and readable synthesis of the latest advances in cell biology, helping specialists stay current with the rapidly evolving field. Expert authors contribute to the journal by annotating and highlighting the most significant papers from the extensive body of research published annually, offering valuable insights and saving time for readers by distilling key findings. COCEBI is part of the Current Opinion and Research (CO+RE) suite of journals, which leverages the legacy of editorial excellence, high impact, and global reach to ensure that the journal is a widely read resource integral to scientists' workflow. It is published by Elsevier, a publisher known for its commitment to excellence in scientific publishing and the communication of reproducible biomedical research aimed at improving human health. The journal's content is designed to be an invaluable resource for a diverse audience, including researchers, lecturers, teachers, professionals, policymakers, and students.