Department of Biochemistry, School of Life Sciences, University of Hyderabad, Hyderabad, India.
RNA Biol. 2023 Jan;20(1):95-108. doi: 10.1080/15476286.2023.2192552.
Telomeres are terminal structures that define the ends of linear chromosomes. They harbour specialized ribonucleoprotein complexes which play a major role in genome integrity by preventing unscheduled DNA damage repair events. Genes located adjacent to telomere repeat sequences are repressed by a phenomenon called telomere position effect (TPE) via epigenetic silencing. RNA surveillance pathways post-transcriptionally regulate any leaky transcripts arising from the telomeres. Recently, multiple non-coding RNA species originate from telomere ends, namely, TERRA (telomeric repeat-containing RNA), ARRET, sub-telomeric XUTs and sub-telomeric CUTs have been identified. In this study, we report a role for the transcription termination complex (Rtt103-Rai1-Rat1) in regulating the abundance of the sub-telomeric transcripts in a transcription-dependent manner. We show that the Rtt103 mutants have elevated levels of TERRA and other sub-telomeric transcripts that are usually silenced. Our study suggests that Rtt103 potentially recruits the exonuclease, Rat1 in a RNA polymerase II dependent manner to degrade these transcripts and regulate their levels in the cell.
端粒是线性染色体末端的结构。它们包含特殊的核糖核蛋白复合物，通过防止非计划性的 DNA 损伤修复事件，在维持基因组完整性方面发挥主要作用。邻近端粒重复序列的基因通过一种称为端粒位置效应（TPE）的表观遗传沉默机制受到抑制。RNA 监测途径通过转录后调控从端粒产生的任何渗漏转录本。最近，多种非编码 RNA 从端粒末端起源，即 TERRA（端粒重复 RNA）、ARRET、亚端粒 XUT 和亚端粒 CUT。在这项研究中，我们报告了转录终止复合物（Rtt103-Rai1-Rat1）在转录依赖性方式下调节亚端粒转录本丰度的作用。我们表明，Rtt103 突变体中端粒重复 RNA 和其他通常被沉默的亚端粒转录本的水平升高。我们的研究表明，Rtt103 可能以 RNA 聚合酶 II 依赖的方式招募外切酶 Rat1 来降解这些转录本并调节它们在细胞中的水平。
