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PP4 dephosphorylates Maf1 to couple multiple stress conditions to RNA polymerase III repression

Andrew J Oler1, Bradley R Cairns

  • 1HHMI, Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA.

The EMBO Journal
|February 16, 2012
PubMed

Insights

The protein phosphatase 4 (PP4) complex directly dephosphorylates Maf1, a key repressor of RNA polymerase III (Pol III) transcription. This action is crucial for regulating Pol III activity under stress conditions in yeast.

Area of Science:

  • Molecular Biology
  • Cellular Regulation

Background:

  • Maf1 acts as a master repressor of RNA polymerase III (Pol III) transcription in eukaryotes.
  • Maf1 integrates cellular signals, becoming dephosphorylated and accumulating in the nucleus under unfavorable conditions to repress Pol III transcription.

Purpose of the Study:

  • To identify the primary phosphatase responsible for Maf1 dephosphorylation.
  • To elucidate the role of this phosphatase complex in regulating Maf1's function and Pol III transcription.

Main Methods:

  • Co-immunoprecipitation assays to identify interacting proteins.
  • In vitro dephosphorylation assays using purified proteins.
  • Analysis of Maf1 dephosphorylation and nuclear localization under various stress conditions.

Main Results:

  • The protein phosphatase 4 (PP4) complex, comprising subunits Pph3, Psy2, Rrd1, and Tip41, was identified as the main Maf1 phosphatase.
  • PP4 directly dephosphorylates Maf1 in vitro and mediates its nuclear accumulation and repression of Pol III transcription in response to stress.
  • The catalytic subunit Pph3 is essential for stress-induced Maf1 dephosphorylation.

Conclusions:

  • PP4 is the principal phosphatase regulating Maf1 activity.
  • PP4 plays a critical role in integrating cellular stress and nutritional status to control Pol III transcription via Maf1.
  • This finding highlights PP4 as a key mediator of cellular stress responses affecting transcription.

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