Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
PLoS Genet. 2011 Sep;7(9):e1002273. doi: 10.1371/journal.pgen.1002273. Epub 2011 Sep 8.
Transcriptome dynamics is governed by two opposing processes, mRNA production and degradation. Recent studies found that changes in these processes are frequently coordinated and that the relationship between them shapes transcriptome kinetics. Specifically, when transcription changes are counter-acted with changes in mRNA stability, transient fast-relaxing transcriptome kinetics is observed. A possible molecular mechanism underlying such coordinated regulation might lay in two RNA polymerase (Pol II) subunits, Rpb4 and Rpb7, which are recruited to mRNAs during transcription and later affect their degradation in the cytoplasm. Here we used a yeast strain carrying a mutant Pol II which poorly recruits these subunits. We show that this mutant strain is impaired in its ability to modulate mRNA stability in response to stress. The normal negative coordinated regulation is lost in the mutant, resulting in abnormal transcriptome profiles both with respect to magnitude and kinetics of responses. These results reveal an important role for Pol II, in regulation of both mRNA synthesis and degradation, and also in coordinating between them. We propose a simple model for production-degradation coupling that accounts for our observations. The model shows how a simple manipulation of the rates of co-transcriptional mRNA imprinting by Pol II may govern genome-wide transcriptome kinetics in response to environmental changes.
转录组动态受两个相反的过程控制,即 mRNA 的产生和降解。最近的研究发现,这些过程的变化经常是协调的,它们之间的关系决定了转录组动力学。具体来说,当转录变化与 mRNA 稳定性变化相抗衡时,会观察到短暂的快速松弛转录组动力学。这种协调调控的可能分子机制可能在于两种 RNA 聚合酶 (Pol II) 亚基,Rpb4 和 Rpb7,它们在转录过程中被招募到 mRNA 上,然后在细胞质中影响其降解。在这里,我们使用了一种携带突变 Pol II 的酵母菌株,该突变体很难招募这些亚基。我们表明,这种突变菌株在调节 mRNA 稳定性以应对应激方面存在缺陷。在突变体中,正常的负协调调控丢失,导致响应的幅度和动力学的异常转录组谱。这些结果揭示了 Pol II 在调节 mRNA 合成和降解以及协调两者方面的重要作用。我们提出了一个简单的生产-降解偶联模型,该模型解释了我们的观察结果。该模型展示了 Pol II 对共转录 mRNA 印记的速率的简单操纵如何控制对环境变化的全基因组转录组动力学。