Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, Alabama 35294-0024, USA.
J Biol Chem. 2010 May 7;285(19):14152-9. doi: 10.1074/jbc.M110.115220. Epub 2010 Mar 18.
The rate of ribosome synthesis is proportional to the rate of cell proliferation; thus, transcription of rRNA by RNA polymerase I (Pol I) is an important target for the regulation of this process. Most previous investigations into mechanisms that regulate the rate of ribosome synthesis have focused on the initiation step of transcription by Pol I; however, recent studies in yeast and mammals have identified factors that influence transcription elongation by Pol I. The RNA polymerase-associated factor 1 complex (Paf1C) is a transcription elongation factor with known roles in Pol II transcription. We previously identified a role for Paf1C in transcription elongation by Pol I. In this study, genetic interactions between genes for Paf1C and Pol I subunits confirm this conclusion. In vitro studies demonstrate that purified Paf1C directly increases the rate of transcription elongation by Pol I. Finally, we show that Paf1C function is required for efficient control of Pol I transcription in response to target of rapamycin (TOR) signaling or amino acid limitation. These studies demonstrate that Paf1C plays an important direct role in cellular control of rRNA expression.
核糖体合成的速度与细胞增殖的速度成正比;因此,RNA 聚合酶 I(Pol I)对 rRNA 的转录是调节该过程的重要目标。大多数先前关于调节核糖体合成速度的机制的研究都集中在 Pol I 转录的起始步骤上;然而,最近在酵母和哺乳动物中的研究已经确定了影响 Pol I 转录延伸的因素。RNA 聚合酶相关因子 1 复合物(Paf1C)是一种转录延伸因子,在 Pol II 转录中具有已知的作用。我们之前确定了 Paf1C 在 Pol I 转录延伸中的作用。在这项研究中,Paf1C 和 Pol I 亚基基因之间的遗传相互作用证实了这一结论。体外研究表明,纯化的 Paf1C 可直接增加 Pol I 的转录延伸速度。最后,我们表明 Paf1C 功能对于有效控制 Pol I 转录以响应雷帕霉素(TOR)信号或氨基酸限制是必需的。这些研究表明,Paf1C 在细胞对 rRNA 表达的控制中起着重要的直接作用。