General decapping activators target different subsets of inefficiently translated mRNAs
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.
Data availability
The data discussed in this publication have been deposited in NCBI's Gene Expression Omnibus and are accessible through GEO Series accession number GSE107841 at the link https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE107841.
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Genome-wilde identification of decapping substrates in the yeast Saccharomyces cervisiaeNCBI Gene Expression Omnibus, GSE107841.
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Ribosome profiling study of rli1 depeletion strainNCBI Gene Expression Omnibus, GSE69414.
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Widespread Co-translational RNA Decay Reveals Ribosome DynamicsNCBI Gene Expression Omnibus, GSE63120.
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A High Resolution Profile of NMD Substrates in YeastNCBI Gene Expression Omnibus, GSE86428.
Article and author information
Author details
Funding
National Institutes of Health (5R01 GM27757-37)
- Allan Jacobson
National Institutes of Health (1R35GM122468- 01)
- Allan Jacobson
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2018, He et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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