General decapping activators target different subsets of inefficiently translated mRNAs

Abstract
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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.

The following data sets were generated

1. He F
2. Celik A
(2017) Genome-wilde identification of decapping substrates in the yeast Saccharomyces cervisiae
NCBI Gene Expression Omnibus, GSE107841.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE107841

The following previously published data sets were used

1. Young DJ
2. Guydosh NR
3. Zhang F
4. Hinnebusch AG
5. Green R
(2015) Ribosome profiling study of rli1 depeletion strain
NCBI Gene Expression Omnibus, GSE69414.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE69414
(2015) Widespread Co-translational RNA Decay Reveals Ribosome Dynamics
NCBI Gene Expression Omnibus, GSE63120.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE63120
1. Celik A
2. Baker R
3. He F
4. Jacobson A
(2016) A High Resolution Profile of NMD Substrates in Yeast
NCBI Gene Expression Omnibus, GSE86428.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE86428

Article and author information

Author details

Feng He

Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, United States

For correspondence
feng.he@umassmed.edu

Competing interests
The authors declare that no competing interests exist.
Alper Celik

Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, United States

Competing interests
The authors declare that no competing interests exist.
Chan Wu

Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, United States

Competing interests
The authors declare that no competing interests exist.
Allan Jacobson

Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, United States

For correspondence
Allan.Jacobson@umassmed.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-5661-3821

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

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.