Telomeric repeat-containing RNA (TERRA) molecules play important roles at telomeres, from heterochromatin regulation to telomerase activity control. In human cells, TERRA is transcribed from subtelomeric promoters located on most chromosome ends and associates with telomeres. The origin of mouse TERRA molecules is however unclear, as transcription from the pseudoautosomal PAR locus was recently suggested to account for the vast majority of TERRA in embryonic stem cells (ESC). Here, we confirm the production of TERRA from both the chromosome 18q telomere and the PAR locus in mouse embryonic fibroblasts, ESC and various mouse cancer and immortalized cell lines, and we identify two novel sources of TERRA on mouse chromosome 2 and X. Using various approaches, we show that PAR-TERRA molecules account for the majority of TERRA transcripts, displaying an increase of 2 to 4 orders of magnitude compared to the telomeric 18q transcript. Finally, we present a SILAC-based pull-down screen revealing a large overlap between TERRA-interacting proteins in human and mouse cells, including PRC2 complex subunits, chromatin remodeling factors, DNA replication proteins, Aurora kinases, shelterin complex subunits, Bloom helicase, Coilin and paraspeckle proteins. Hence, despite originating from distinct genomic regions, mouse and human TERRA are likely to play similar functions in cells.

中文翻译：

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PAR-TERRA 是正常和癌症小鼠细胞中含有端粒重复序列的 RNA 转录的主要贡献者

含有端粒重复序列的 RNA (TERRA) 分子在端粒中发挥着重要作用，从异染色质调节到端粒酶活性控制。在人类细胞中，TERRA 从位于大多数染色体末端并与端粒相关联的亚端粒启动子转录。然而，小鼠 TERRA 分子的起源尚不清楚，因为最近有人认为来自假常染色体 PAR 基因座的转录是胚胎干细胞 (ESC) 中绝大多数 TERRA 的原因。在这里，我们确认了 TERRA 从染色体 18q 端粒和小鼠胚胎成纤维细胞、ESC 和各种小鼠癌症和永生化细胞系中的 PAR 基因座产生，并且我们在小鼠染色体 2 和 X 上鉴定了两种新的 TERRA 来源。方法，我们表明 PAR-TERRA 分子占 TERRA 转录本的大部分，显示与端粒 18q 转录本相比增加了 2 到 4 个数量级。最后，我们展示了一个基于 SILAC 的下拉屏幕，揭示了人和小鼠细胞中 TERRA 相互作用蛋白之间的大量重叠，包括 PRC2 复合亚基、染色质重塑因子、DNA 复制蛋白、Aurora 激酶、shelterin 复合亚基、Bloom 解旋酶、 Coilin 和 paraspeckle 蛋白。因此，尽管来自不同的基因组区域，小鼠和人类 TERRA 可能在细胞中发挥相似的功能。Aurora 激酶、shelterin 复合亚基、Bloom 解旋酶、Coilin 和 paraspeckle 蛋白。因此，尽管来自不同的基因组区域，小鼠和人类 TERRA 可能在细胞中发挥相似的功能。Aurora 激酶、shelterin 复合亚基、Bloom 解旋酶、Coilin 和 paraspeckle 蛋白。因此，尽管来自不同的基因组区域，小鼠和人类 TERRA 可能在细胞中发挥相似的功能。