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Numerous Post-Translational Modifications of RNA Polymerase II Subunit Rpb4 Link Transcription to Post-Transcriptional Mechanisms

49 Pages Posted: 16 Sep 2019 Sneak Peek Status: Under Review

See all articles by Stephen Richard

Stephen Richard

Technion-Israel Institute of Technology - Department of Molecular Microbiology

Lital Gross Gross

Technion-Israel Institute of Technology - Department of Molecular Microbiology

Jonathan Fischer

University of California, Berkeley - Computer Science Division

Keren Bendalak

Technion-Israel Institute of Technology - Smoler Proteomics Center

Tamar Ziv

Technion-Israel Institute of Technology - Smoler Proteomics Center

Shira Urim

Technion-Israel Institute of Technology - Department of Molecular Microbiology

Mordechai Choder

Technion-Israel Institute of Technology - Department of Molecular Microbiology

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Abstract

Rpb4/7 binds RNA Polymerase II (Pol II) transcripts co-transcriptionally and accompanies them throughout their lives. By virtue of its capacity to interact with key regulators (e.g., Pol II, eIF3, Pat1) both temporarily and spatially, Rpb4/7 regulates the major stages of the mRNA lifecycle. Here we show that Rpb4/7 can undergo over 100 combinations of post-translational modifications (PTMs). Remarkably, the Rpb4/7 PTMs repertoire changes as the mRNA/Rpb4/7 complex progresses from one stage to the next. A mutagenesis approach in residues that undergo PTMs suggests that temporal Rpb4 PTMs regulate its interactions with key regulators of gene expression that control transcriptional and post-transcriptional stages. Moreover, one mutant type specifically affects mRNA synthesis despite its normal association with Pol II, whereas the other affects both 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. Taken together, we propose that temporal Rpb4/7 PTMs are involved in cross talks among the various stages of the mRNA lifecycle.

Keywords: mRNA buffering, Post-translational modifications, mRNA synthesis and decay, Pol II subunit Rpb4/7

Suggested Citation

Richard, Stephen and Gross, Lital Gross and Fischer, Jonathan and Bendalak, Keren and Ziv, Tamar and Urim, Shira and Choder, Mordechai, Numerous Post-Translational Modifications of RNA Polymerase II Subunit Rpb4 Link Transcription to Post-Transcriptional Mechanisms (September 12, 2019). CELL-REPORTS-D-19-03368. Available at SSRN: https://ssrn.com/abstract=3452789 or http://dx.doi.org/10.2139/ssrn.3452789
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Stephen Richard

Technion-Israel Institute of Technology - Department of Molecular Microbiology ( email )

Israel

Lital Gross Gross

Technion-Israel Institute of Technology - Department of Molecular Microbiology

Israel

Jonathan Fischer

University of California, Berkeley - Computer Science Division

Berkeley, CA 94720-1712
United States

Keren Bendalak

Technion-Israel Institute of Technology - Smoler Proteomics Center

Israel

Tamar Ziv

Technion-Israel Institute of Technology - Smoler Proteomics Center

Israel

Shira Urim

Technion-Israel Institute of Technology - Department of Molecular Microbiology

Israel

Mordechai Choder (Contact Author)

Technion-Israel Institute of Technology - Department of Molecular Microbiology ( email )

Israel

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