General decapping activators target different subsets of inefficiently translated mRNAs

Elife. 2018 Dec 6:7:e34409. doi: 10.7554/eLife.34409.

Abstract

The Dcp1-Dcp2 decapping enzyme and the decapping activators Pat1, Dhh1, and Lsm1 regulate mRNA decapping, but their mechanistic integration is unknown. We analyzed the gene expression consequences of deleting PAT1, LSM1, or DHH1, or the DCP2 C-terminal domain, and found that: i) the Dcp2 C-terminal domain is an effector of both negative and positive regulation; ii) rather than being global activators of decapping, Pat1, Lsm1, and Dhh1 directly target specific subsets of yeast mRNAs and loss of the functions of each of these factors has substantial indirect consequences for genome-wide mRNA expression; and iii) transcripts targeted by Pat1, Lsm1, and Dhh1 exhibit only partial overlap, are generally translated inefficiently, and, as expected, are targeted to decapping-dependent decay. Our results define the roles of Pat1, Lsm1, and Dhh1 in decapping of general mRNAs and suggest that these factors may monitor mRNA translation and target unique features of individual mRNAs.

Keywords: Dcp1-Dcp2; S. cerevisiae; chromosomes; decapping activators; decapping enzyme; gene expression; mRNA decay; mRNA translation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • DEAD-box RNA Helicases / genetics*
  • Endoribonucleases / genetics
  • Gene Expression Regulation, Fungal
  • Protein Biosynthesis / genetics*
  • RNA Cap-Binding Proteins / genetics*
  • RNA Stability / genetics
  • RNA, Messenger / genetics
  • RNA-Binding Proteins / genetics*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins / genetics*

Substances

  • LSM1 protein, S cerevisiae
  • PAT1 protein, S cerevisiae
  • RNA Cap-Binding Proteins
  • RNA, Messenger
  • RNA-Binding Proteins
  • Saccharomyces cerevisiae Proteins
  • mRNA decapping enzymes
  • DCP1 protein, S cerevisiae
  • DCP2 protein, S cerevisiae
  • Endoribonucleases
  • DHH1 protein, S cerevisiae
  • DEAD-box RNA Helicases