Luke Brian, Lingner Joachim
EPFL-Ecole Polytechnique Fédérale de Lausanne, ISREC-Swiss Institute for Experimental Cancer Research, Lausanne, Switzerland.
EMBO J. 2009 Sep 2;28(17):2503-10. doi: 10.1038/emboj.2009.166. Epub 2009 Jul 23.
Telomeres, the physical ends of eukaryotic chromosomes, consist of tandem arrays of short DNA repeats and a large set of specialized proteins. A recent analysis has identified telomeric repeat-containing RNA (TERRA), a large non-coding RNA in animals and fungi, which forms an integral component of telomeric heterochromatin. TERRA transcription occurs at most or all chromosome ends and it is regulated by RNA surveillance factors and in response to changes in telomere length. TERRA functions that are emerging suggest important roles in the regulation of telomerase and in orchestrating chromatin remodelling throughout development and cellular differentiation. The accumulation of TERRA at telomeres can also interfere with telomere replication, leading to a sudden loss of telomere tracts. Such a phenotype can be observed upon impairment of the RNA surveillance machinery or in cells from ICF (Immunodeficiency, Centromeric region instability, Facial anomalies) patients, in which TERRA is upregulated because of DNA methylation defects in the subtelomeric region. Thus, TERRA may mediate several crucial functions at the telomeres, a region of the genome that had been considered to be transcriptionally silent.
端粒是真核生物染色体的物理末端，由短DNA重复序列的串联阵列和大量特殊蛋白质组成。最近的一项分析鉴定出了含端粒重复序列的RNA（TERRA），这是一种存在于动物和真菌中的大型非编码RNA，它是端粒异染色质的一个组成部分。TERRA转录发生在大多数或所有染色体末端，并且受RNA监测因子调控以及响应端粒长度的变化。新出现的TERRA功能表明其在端粒酶调控以及在整个发育和细胞分化过程中协调染色质重塑方面发挥重要作用。TERRA在端粒处的积累也会干扰端粒复制，导致端粒序列突然丢失。在RNA监测机制受损时或在ICF（免疫缺陷、着丝粒区域不稳定、面部异常）患者的细胞中可以观察到这种表型，在这些患者中，由于亚端粒区域的DNA甲基化缺陷，TERRA表达上调。因此，TERRA可能在端粒处介导几种关键功能，而端粒这个基因组区域曾被认为是转录沉默的。
