Numerous Post-translational Modifications of RNA Polymerase II Subunit Rpb4/7 Link Transcription to Post-transcriptional Mechanisms

• Published in: Cell reports (Cambridge) 2021-01, Vol.34 (2), p.108578-108578, Article 108578
• Main Authors: Richard, Stephen, Gross, Lital, Fischer, Jonathan, Bendalak, Keren, Ziv, Tamar, Urim, Shira, Choder, Mordechai
• Format: Article
• Language: English
• Subjects: Animals; mRNA buffering; mRNA imprinting; mRNA lifecycle; post-translational modifications; Protein Processing, Post-Translational; RNA Polymerase II - metabolism; Rpb4/7; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - metabolism; yeast
• ISSN: 2211-1247; 2211-1247
• 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. [Display omitted] •More than 100 possible combinations of various PTMs are identified in Rpb4/7•PTMs change temporally during the various stages of Rpb4/7/mRNA life cycle•E-rich loop of Rpb4 involved in PTM-regulated binding of RNA processing factors•Mutations that mimic methylation of this E-rich loop affect mRNA buffering Rpb4/7 mediates mRNA synthesis, transport, translation, and decay through “mRNA imprinting.” Richard et al. now show that Rpb4/7 undergoes more than 100 possible combinations of post-translational modifications that change temporally and spatially. These modifications seem to represent a language by which the above stages of the mRNA life cycle communicate.