TERRA transcripts are bound by a complex array of RNA-binding proteins
TERRA transcripts are bound by a complex array of RNA-binding proteins
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DOI：
10.1038/ncomms1032
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发表时间：
2010-06-01
影响因子：
16.6
通讯作者：
Blasco, Maria A.
中科院分区：
文献类型：
--
作者：
Lopez de Silanes, Isabel;Stagno d'Alcontres, Martina;Blasco, Maria A.
端粒是从端粒富含C的链转录而来的，产生了含有UUAGGG重复序列的端粒转录本或Terra，这是端粒的新结构成分。Terra的丰度高度依赖于发育状态(包括核重编程)、端粒长度、细胞压力、肿瘤分期和染色质结构。然而，控制Terra水平的分子机制和因素在很大程度上仍不清楚。在这项研究中，我们确定了一组RNA结合蛋白，它们在原代小鼠胚胎成纤维细胞中内源性结合和调节Terra。通过生物素下拉分析和LC-MALDI TOF/TOF质谱仪进行鉴定。异质核糖核蛋白家族的不同成员属于与Terra结合更丰富的核糖核蛋白家族。小干扰RNA下调Terra结合的限制性商业惯例进一步表明，它们可以影响Terra的丰度、它们的位置和端粒的延长。这些发现预测了与Terra相关的限制性商业惯例对端粒生物学和端粒疾病(如癌症和衰老)的影响。
Telomeres are transcribed from the telomeric C-rich strand, giving rise to UUAGGG repeat-containing telomeric transcripts or TERRA, which are novel structural components of telomeres. TERRA abundance is highly dependent on developmental status (including nuclear reprogramming), telomere length, cellular stresses, tumour stage and chromatin structure. However, the molecular mechanisms and factors controlling TERRA levels are still largely unknown. In this study, we identify a set of RNA-binding proteins, which endogenously bind and regulate TERRA in the context of primary mouse embryonic fibroblasts. The identification was carried out by biotin pull-down assays followed by LC-MALDI TOF/TOF mass spectrometry. Different members of the heterogeneous nuclear ribonucleoprotein family are among the ribonucleoprotein family that bind more abundantly to TERRA. Downregulation of TERRA-bound RBPs by small interfering RNA further shows that they can impact on TERRA abundance, their location and telomere lengthening. These findings anticipate an impact of TERRA-associated RBPs on telomere biology and telomeres diseases, such as cancer and aging.