Telomeric repeat-containing RNA and RNA surveillance factors at mammalian chromosome ends
Telomeric repeat-containing RNA and RNA surveillance factors at mammalian chromosome ends
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DOI：
10.1126/science.1147182
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发表时间：
2007-11-02
期刊：
影响因子：
56.9
通讯作者：
Lingner, Joachim
中科院分区：
文献类型：
--
作者：
Azzalin, Claus M.;Reichenbach, Patrick;Lingner, Joachim
端粒是位于真核生物线性染色体末端的DNA-蛋白质复合体，对染色体的稳定性至关重要。到目前为止，端粒一直被认为是转录沉默的。我们证明哺乳动物的端粒被转录成含有端粒重复序列的RNA(Terra)。Terra分子的长度是不同的，从几个亚端粒基因座转录到染色体末端，并定位于端粒。我们还发现，生殖器形态发生缺陷(SMG)蛋白是无义介导的信使RNA衰退的效应蛋白，在体内富含在端粒，负调控Terra与染色质的结合，并保护染色体末端免受端粒丢失。因此，端粒被活跃地转录成Terra，SMG因子代表了Terra调控和维持端粒完整性之间的分子联系。
Telomeres, the DNA-protein complexes located at the end of linear eukaryotic chromosomes, are essential for chromosome stability. Until now, telomeres have been considered to be transcriptionally silent. We demonstrate that mammalian telomeres are transcribed into telomeric repeat-containing RNA (TERRA). TERRA molecules are heterogeneous in length, are transcribed from several subtelomeric loci toward chromosome ends, and localize to telomeres. We also show that suppressors with morphogenetic defects in genitalia (SMG) proteins, which are effectors of nonsense-mediated messenger RNA decay, are enriched at telomeres in vivo, negatively regulate TERRA association with chromatin, and protect chromosome ends from telomere loss. Thus, telomeres are actively transcribed into TERRA, and SMG factors represent a molecular link between TERRA regulation and the maintenance of telomere integrity.