Institute for Cell and Molecular Biosciences, Newcastle University Medical School, Newcastle upon Tyne NE2 4HH, UK.
Nucleic Acids Res. 2018 Jan 25;46(2):621-634. doi: 10.1093/nar/gkx1131.
The conserved PAF1 complex (Cdc73, Paf1, Ctr9, Leo1 and Rtf1, in yeast), binds RNA pol II, and affects levels of many RNAs. Although PAF1 is a complex, there is evidence that different components perform different functions. In yeast, Cdc73, Paf1 and Ctr9 maintain normal telomerase RNA (TLC1) levels and affect telomere length. Here we report a new connection between the PAF1 complex and telomere biology. We show that Paf1 and Ctr9 maintain low telomere repeat containing RNA (TERRA) levels while Cdc73, Leo1 and Rtf1 have lesser effects. Analysis of double mutants shows that Paf1 and Ctr9 can affect TERRA independently of Sir4, Rat1, and Trf4, previously identified regulators of TERRA. The data suggest that Paf1 and Ctr9 maintain low TERRA levels by affecting both transcription and degradation and that short telomeres in cdc73Δ, paf1Δ and ctr9Δ mutants do not induce TERRA. These data establish the PAF1 complex as a new regulator of TERRA, and are consistent with the model in which Paf1 and Ctr9, the core components of the PAF1 complex, affect transcript levels and cell fitness by numerous mechanisms.
保守的 PAF1 复合物（酵母中的 Cdc73、Paf1、Ctr9、Leo1 和 Rtf1）与 RNA pol II 结合，并影响许多 RNA 的水平。尽管 PAF1 是一个复合物，但有证据表明不同的组件执行不同的功能。在酵母中，Cdc73、Paf1 和 Ctr9 维持正常的端粒酶 RNA（TLC1）水平并影响端粒长度。在这里，我们报告了 PAF1 复合物与端粒生物学之间的新联系。我们表明，Paf1 和 Ctr9 维持低端粒重复 RNA（TERRA）水平，而 Cdc73、Leo1 和 Rtf1 的影响较小。双突变体分析表明，Paf1 和 Ctr9 可以独立于先前鉴定的 TERRA 调节因子 Sir4、Rat1 和 Trf4 来影响 TERRA。数据表明，Paf1 和 Ctr9 通过影响转录和降解来维持低 TERRA 水平，并且在 cdc73Δ、paf1Δ 和 ctr9Δ 突变体中较短的端粒不会诱导 TERRA。这些数据确立了 PAF1 复合物作为 TERRA 的新调节剂，并且与模型一致，即 PAF1 复合物的核心组件 Paf1 和 Ctr9 通过多种机制影响转录水平和细胞适应性。
