Institute of Biochemistry, Eidgenössische Technische Hochschule Zürich, CH-8093 Zürich, Switzerland.
RNA. 2012 Apr;18(4):684-93. doi: 10.1261/rna.029587.111. Epub 2012 Feb 22.
Telomeres are nucleoprotein structures capping the physical ends of linear eukaryotic chromosomes. Although largely heterochromatic, telomeres are transcribed into telomeric repeat-containing RNA (TERRA) molecules by RNA polymerase II. The functions associated with telomere transcription and TERRA remain ill defined. Here we show that the transcriptional activity of human telomeres directly regulates their movement during interphase. We find that chemical inhibition of global transcription dampens telomere motion, while global stimulation promotes it. Likewise, when DNA methyltransferase enzymes are deleted to augment telomere transcription, we observe increased telomere movement. Finally, using a cell line engineered with a unique transcriptionally inducible telomere, we show that transcription of one specific telomere stimulates only its own dynamics without overtly affecting its stability or its length. We reveal a new and unforeseen function for telomere transcription as a regulator of telomere motion, and speculate on the intriguing possibility that transcription-dependent telomere motion sustains the maintenance of functional and dysfunctional telomeres.
端粒是线性真核染色体物理末端的核蛋白结构。尽管端粒主要是异染色质，但它们可以被 RNA 聚合酶 II 转录为含有端粒重复的 RNA（TERRA）分子。与端粒转录和 TERRA 相关的功能仍未明确。在这里，我们表明人类端粒的转录活性直接调节它们在间期的运动。我们发现，化学抑制全局转录会抑制端粒运动，而全局刺激则会促进端粒运动。同样，当删除 DNA 甲基转移酶酶以增强端粒转录时，我们观察到端粒运动增加。最后，我们使用一种带有独特转录诱导端粒的细胞系进行实验，结果表明，一个特定端粒的转录仅刺激其自身的动力学，而不会明显影响其稳定性或长度。我们揭示了端粒转录作为端粒运动调节剂的新的、意想不到的功能，并推测转录依赖性端粒运动可能维持功能和非功能端粒的维持。
