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

Stephen Richard; Lital Gross; Jonathan Fischer; Keren Bendalak; Tamar Ziv; Shira Urim; Mordechai Choder

doi:10.1016/j.celrep.2020.108578

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

Cell Rep. 2021 Jan 12;34(2):108578. doi: 10.1016/j.celrep.2020.108578.

Authors

Stephen Richard¹, Lital Gross¹, Jonathan Fischer², Keren Bendalak³, Tamar Ziv³, Shira Urim¹, Mordechai Choder⁴

Affiliations

¹ Department of Molecular Microbiology, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096, Israel.
² Computer Science Division, University of California, Berkeley, Berkeley, CA 94720, USA.
³ Smoler Proteomics Center, Faculty of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel.
⁴ Department of Molecular Microbiology, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096, Israel. Electronic address: choder@technion.ac.il.

PMID: 33440147
DOI: 10.1016/j.celrep.2020.108578

Abstract

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.

Keywords: Rpb4/7; mRNA buffering; mRNA imprinting; mRNA lifecycle; post-translational modifications; yeast.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Protein Processing, Post-Translational
RNA Polymerase II / metabolism*
Saccharomyces cerevisiae / metabolism*
Saccharomyces cerevisiae Proteins / metabolism*

Substances

Saccharomyces cerevisiae Proteins
RNA Polymerase II
RPB4 protein, S cerevisiae
RPB7 protein, S cerevisiae