P-body proteins regulate transcriptional rewiring to promote DNA replication stress resistance

Nat Commun. 2017 Sep 15;8(1):558. doi: 10.1038/s41467-017-00632-2.

Abstract

mRNA-processing (P-) bodies are cytoplasmic granules that form in eukaryotic cells in response to numerous stresses to serve as sites of degradation and storage of mRNAs. Functional P-bodies are critical for the DNA replication stress response in yeast, yet the repertoire of P-body targets and the mechanisms by which P-bodies promote replication stress resistance are unknown. In this study we identify the complete complement of mRNA targets of P-bodies during replication stress induced by hydroxyurea treatment. The key P-body protein Lsm1 controls the abundance of HHT1, ACF4, ARL3, TMA16, RRS1 and YOX1 mRNAs to prevent their toxic accumulation during replication stress. Accumulation of YOX1 mRNA causes aberrant downregulation of a network of genes critical for DNA replication stress resistance and leads to toxic acetaldehyde accumulation. Our data reveal the scope and the targets of regulation by P-body proteins during the DNA replication stress response.P-bodies form in response to stress and act as sites of mRNA storage and degradation. Here the authors identify the mRNA targets of P-bodies during DNA replication stress, and show that P-body proteins act to prevent toxic accumulation of these target transcripts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-Ribosylation Factors / genetics
  • Cell Cycle Proteins / genetics
  • Cytoplasmic Granules / metabolism
  • DNA Replication / genetics*
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation*
  • Homeodomain Proteins / genetics
  • Hydroxyurea / pharmacology
  • Nuclear Proteins / genetics
  • RNA Cap-Binding Proteins / genetics*
  • RNA, Messenger / metabolism*
  • Repressor Proteins / genetics
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins / genetics*
  • Stress, Physiological / genetics*

Substances

  • Cell Cycle Proteins
  • Enzyme Inhibitors
  • Homeodomain Proteins
  • LSM1 protein, S cerevisiae
  • Nuclear Proteins
  • RNA Cap-Binding Proteins
  • RNA, Messenger
  • RRS1 protein, S cerevisiae
  • Repressor Proteins
  • Saccharomyces cerevisiae Proteins
  • Yox1 protein, S cerevisiae
  • ADP-Ribosylation Factors
  • ARL3 protein, S cerevisiae
  • Hydroxyurea