Gong Yi, Liu Yie
Laboratory of Genetics and Genomics, National Institute on Aging/National Institutes of Health, 251 Bayview Blvd, Baltimore, MD 21224, USA.
Cancers (Basel). 2023 Apr 6;15(7):2178. doi: 10.3390/cancers15072178.
Telomeric repeat containing RNA (TERRA) is transcribed from subtelomeric regions to telomeres. TERRA RNA can invade telomeric dsDNA and form telomeric R-loop structures. A growing body of evidence suggests that TERRA-mediated R-loops are critical players in telomere length homeostasis. Here, we will review current knowledge on the regulation of R-loop levels at telomeres. In particular, we will discuss how the central player TERRA and its binding proteins modulate R-loop levels through various mechanisms. We will further provide an overview of the consequences of TERRA-mediated persistent or unscheduled R-loops at telomeres in human ALT cancers and other organisms, with a focus on telomere length regulation after replication interference-induced damage and DNA homologous recombination-mediated repair.
端粒重复序列包含RNA（TERRA）从亚端粒区域转录至端粒。TERRA RNA可侵入端粒双链DNA并形成端粒R环结构。越来越多的证据表明，TERRA介导的R环是端粒长度稳态的关键参与者。在此，我们将综述当前关于端粒处R环水平调控的知识。特别地，我们将讨论核心分子TERRA及其结合蛋白如何通过多种机制调节R环水平。我们还将概述TERRA介导的端粒处持续性或非计划性R环在人类端粒酶替代途径（ALT）癌症及其他生物体中的后果，重点关注复制干扰诱导损伤和DNA同源重组介导修复后的端粒长度调控。
