Department of Molecular Microbiology, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096, Israel.
Computer Science Division, University of California, Berkeley, Berkeley, CA 94720, USA.
Cell Rep. 2021 Jan 12;34(2):108578. doi: 10.1016/j.celrep.2020.108578.
Rpb4/7 binds RNA polymerase II (RNA Pol II) transcripts co-transcriptionally and accompanies them throughout their lives. By virtue of its capacity to interact with key regulators (e.g., RNA Pol II, eIF3, and Pat1) temporally and spatially, Rpb4/7 regulates the major stages of the mRNA life cycle. Here we show that Rpb4/7 can undergo more than 100 combinations of post-translational modifications (PTMs). Remarkably, the Rpb4/7 PTM repertoire changes as the mRNA/Rpb4/7 complex progresses from one stage to the next. These temporal PTMs regulate Rpb4 interactions with key regulators of gene expression that control transcriptional and post-transcriptional stages. Moreover, one mutant type specifically affects mRNA synthesis, whereas the other affects mRNA synthesis and decay; both types disrupt the balance between mRNA synthesis and decay ("mRNA buffering") and the cell's capacity to respond to the environment. We propose that temporal Rpb4/7 PTMs mediate the cross-talk among the various stages of the mRNA life cycle.
Rpb4/7 与 RNA 聚合酶 II（RNA Pol II）转录本共转录结合，并伴随它们的整个生命周期。凭借其在时间和空间上与关键调节因子（如 RNA Pol II、eIF3 和 Pat1）相互作用的能力，Rpb4/7 调节 mRNA 生命周期的主要阶段。在这里，我们表明 Rpb4/7 可以经历超过 100 种翻译后修饰（PTMs）的组合。值得注意的是，随着 mRNA/Rpb4/7 复合物从一个阶段进展到下一个阶段，Rpb4/7 的 PTM 谱发生变化。这些时间 PTMs 调节 Rpb4 与控制转录和转录后阶段的基因表达关键调节因子的相互作用。此外，一种突变型专门影响 mRNA 的合成，而另一种则影响 mRNA 的合成和降解；这两种类型都破坏了 mRNA 合成和降解之间的平衡（“mRNA 缓冲”）以及细胞对环境做出反应的能力。我们提出，时间 Rpb4/7 PTMs 介导了 mRNA 生命周期各个阶段之间的串扰。
