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Identification of TERRA locus unveils a telomere protection role through association to nearly all chromosomes

机译:TERRA基因座的鉴定通过与几乎所有染色体的结合揭示了端粒保护作用

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摘要

Telomeric RNAs (TERRAs) are UUAGGG repeat-containing RNAs that are transcribed from the subtelomere towards the telomere. The precise genomic origin of TERRA has remained elusive. Using a whole-genome RNA-sequencing approach, we identify novel mouse transcripts arising mainly from the subtelomere of chromosome 18, and to a lesser extend chromosome 9, that resemble TERRA in several key aspects. Those transcripts contain UUAGGG-repeats and are heterogeneous in size, fluctuate in abundance in a TERRA-like manner during the cell cycle, are bound by TERRA RNA-binding proteins and are regulated in a manner similar to TERRA in response to stress and the induction of pluripotency. These transcripts are also found to associate with nearly all chromosome ends and downregulation of the transcripts that originate from chromosome 18 causes a reduction in TERRA abundance. Interestingly, downregulation of either chromosome 18 transcripts or TERRA results in increased number of telomere dysfunction-induced foci, suggesting a protective role at telomeres.
机译:端粒RNA(TERRA)是含有UUAGGG重复序列的RNA,从端粒亚基转录到端粒。 TERRA的确切基因组起源仍然难以捉摸。使用全基因组RNA测序方法,我们鉴定出主要来自18号染色体的亚端粒以及延伸至较小范围的9号染色体的新型小鼠转录本,在某些关键方面类似于TERRA。这些转录本包含UUAGGG重复序列,大小不均一,在细胞周期中以TERRA样方式大量波动,与TERRA RNA结合蛋白结合,并以类似于TERRA的方式受到压力和诱导的调节。多能性。还发现这些转录本与几乎所有染色体末端相关,并且源自18号染色体的转录本的下调导致TERRA丰度降低。有趣的是,染色体18转录本或TERRA的下调导致端粒功能障碍诱导的病灶数量增加,表明对端粒有保护作用。

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