Moravec Martin, Wischnewski Harry, Bah Amadou, Hu Yan, Liu Na, Lafranchi Lorenzo, King Megan C, Azzalin Claus M
Institute of Biochemistry (IBC), Eidgenössische Technische Hochschule Zürich (ETHZ), Zürich, Switzerland.
Department of Cell Biology, Yale School of Medicine, New Haven, CT, USA.
EMBO Rep. 2016 Jul;17(7):999-1012. doi: 10.15252/embr.201541708. Epub 2016 May 6.
Telomerase-mediated telomere elongation provides cell populations with the ability to proliferate indefinitely. Telomerase is capable of recognizing and extending the shortest telomeres in cells; nevertheless, how this mechanism is executed remains unclear. Here, we show that, in the fission yeast Schizosaccharomyces pombe, shortened telomeres are highly transcribed into the evolutionarily conserved long noncoding RNA TERRA A fraction of TERRA produced upon telomere shortening is polyadenylated and largely devoid of telomeric repeats, and furthermore, telomerase physically interacts with this polyadenylated TERRA in vivo We also show that experimentally enhanced transcription of a manipulated telomere promotes its association with telomerase and concomitant elongation. Our data represent the first direct evidence that TERRA stimulates telomerase recruitment and activity at chromosome ends in an organism with human-like telomeres.
端粒酶介导的端粒延长赋予细胞群体无限增殖的能力。端粒酶能够识别并延长细胞中最短的端粒；然而，这种机制是如何执行的仍不清楚。在这里，我们表明，在裂殖酵母粟酒裂殖酵母中，缩短的端粒会高度转录为进化上保守的长链非编码RNA TERRA。端粒缩短时产生的一部分TERRA会进行多聚腺苷酸化，并且基本上没有端粒重复序列，此外，端粒酶在体内与这种多聚腺苷酸化的TERRA发生物理相互作用。我们还表明，实验性增强的人工端粒转录会促进其与端粒酶的结合以及随之而来的延长。我们的数据代表了首个直接证据，表明在具有类人端粒的生物体中，TERRA刺激端粒酶在染色体末端的募集和活性。
