Through an integration of genomic and proteomic approaches to advance understanding of long noncoding RNAs, we investigate the function of the telomeric transcript, TERRA. By identifying thousands of TERRA target sites in the mouse genome, we demonstrate that TERRA can bind both incisto telomeres and intransto genic targets. We then define a large network of interacting proteins, including epigenetic factors, telomeric proteins, and the RNA helicase, ATRX. TERRA and ATRX share hundreds of target genes and are functionally antagonistic at these loci: whereas TERRA activates, ATRX represses gene expression. At telomeres, TERRA competes with telomeric DNA for ATRX binding, suppresses ATRX localization, and ensures telomeric stability. Depleting TERRA increases telomerase activity and induces telomeric pathologies, including formation of telomere-induced DNA damage foci and loss or duplication of telomeric sequences. We conclude that TERRA functions as an epigenomic modulator intransand as an essential regulator of telomeres incis.

中文翻译：

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TERRA RNA拮抗ATRX并保护端粒

通过整合基因组学和蛋白质组学方法以进一步了解长的非编码RNA，我们研究了端粒转录本TERRA的功能。通过在小鼠基因组中鉴定数千个TERRA靶位点，我们证明TERRA可以结合切入端粒和非转基因靶标。然后，我们定义了一个相互作用蛋白的大型网络，包括表观遗传因子，端粒蛋白和RNA解旋酶ATRX。TERRA和ATRX共享数百个靶基因，并且在这些基因座上具有功能拮抗作用：而TERRA激活时，ATRX抑制基因表达。在端粒上，TERRA与端粒DNA竞争ATRX结合，抑制ATRX定位，并确保端粒稳定性。消耗TERRA会增加端粒酶活性并诱导端粒病变，包括端粒诱导的DNA损伤灶的形成以及端粒序列的丢失或重复。我们得出的结论是，TERRA充当表观基因组调控子，而端粒切齿是必需的调控子。