Département de Biochimie, Université de Montréal, Montréal, QC H3C 3J7, Canada.
Mol Cell. 2013 Sep 26;51(6):780-91. doi: 10.1016/j.molcel.2013.08.029.
Elongation of a short telomere depends on the action of multiple telomerase molecules, which are visible as telomerase RNA foci or clusters associated with telomeres in yeast and mammalian cells. How several telomerase molecules act on a single short telomere is unknown. Herein, we report that the telomeric noncoding RNA TERRA is involved in the nucleation of telomerase molecules into clusters prior to their recruitment at a short telomere. We find that telomere shortening induces TERRA expression, leading to the accumulation of TERRA molecules into a nuclear focus. Simultaneous time-lapse imaging of telomerase RNA and TERRA reveals spontaneous events of telomerase nucleation on TERRA foci in early S phase, generating TERRA-telomerase clusters. This cluster is subsequently recruited to the short telomere from which TERRA transcripts originate during S phase. We propose that telomere shortening induces noncoding RNA expression to coordinate the recruitment and activity of telomerase molecules at short telomeres.
端粒的延长依赖于多个端粒酶分子的作用，这些端粒酶分子在酵母和哺乳动物细胞中可见为与端粒相关的端粒酶 RNA 焦点或簇。几个端粒酶分子如何作用于单个短端粒尚不清楚。在此，我们报告端粒非编码 RNA TERRA 参与了端粒酶分子在招募到短端粒之前形成簇的核成核作用。我们发现端粒缩短诱导 TERRA 的表达，导致 TERRA 分子积累到核焦点中。端粒酶 RNA 和 TERRA 的同步延时成像揭示了早期 S 期端粒酶在 TERRA 焦点上自发成核的事件，产生 TERRA-端粒酶簇。随后，该簇从 S 期产生 TERRA 转录本的短端粒中招募。我们提出，端粒缩短诱导非编码 RNA 表达，以协调短端粒中端粒酶分子的募集和活性。
