Department of Biochemistry and Molecular Medicine, Université de Montréal, Montréal, Canada.
Wiley Interdiscip Rev RNA. 2014 May-Jun;5(3):407-19. doi: 10.1002/wrna.1220. Epub 2014 Feb 12.
Telomeres are nucleoprotein structures that cap the ends of eukaryotic chromosomes, protecting them from degradation and activation of DNA damage response. For this reason, functional telomeres are vital to genome stability. For years, telomeres were assumed to be transcriptionally silent, because of their heterochromatic state. It was only recently shown that, in several organisms, telomeres are transcribed, giving rise to a long noncoding RNA (lncRNA) called telomeric repeat-containing RNA (TERRA). Several lines of evidence now indicate that TERRA molecules play crucial roles in telomere homeostasis and telomere functions. Recent studies have shown that the expression and regulation of TERRA are dynamically controlled by each chromosome end. TERRA has been involved in the regulation of telomere length, telomerase activity, and heterochromatin formation at telomeres. The correct regulation of the telomeric transcripts may be essential to genome stability, and altered TERRA levels associate with tumorigenesis and cellular senescence. Thus, the study of the molecular mechanisms of TERRA biogenesis and function may advance the understanding of telomere-related diseases, including cancer and aging.
端粒是真核染色体末端的核蛋白结构，可保护其免受降解和 DNA 损伤反应的激活。出于这个原因，功能端粒对于基因组稳定性至关重要。多年来，由于端粒的异染色质状态，人们一直认为端粒是转录沉默的。直到最近才表明，在几种生物体中，端粒被转录，产生一种称为端粒重复 RNA（TERRA）的长非编码 RNA（lncRNA）。现在有几条证据表明，TERRA 分子在端粒稳态和端粒功能中发挥着关键作用。最近的研究表明，TERRA 的表达和调节受到每个染色体末端的动态控制。TERRA 参与了端粒长度、端粒酶活性和端粒异染色质形成的调节。端粒转录物的正确调节对于基因组稳定性至关重要，而改变的 TERRA 水平与肿瘤发生和细胞衰老有关。因此，研究 TERRA 生物发生和功能的分子机制可能有助于深入了解与端粒相关的疾病，包括癌症和衰老。
