Decapping factor Dcp2 controls mRNA abundance and translation to adjust metabolism and filamentation to nutrient availability

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Abstract

Degradation of most yeast mRNAs involves decapping by Dcp1/Dcp2. DEAD-box protein Dhh1 has been implicated as an activator of decapping, in coupling codon non-optimality to enhanced degradation, and as a translational repressor, but its functions in cells are incompletely understood. RNA-Seq analyses coupled with CAGE sequencing of all capped mRNAs revealed increased abundance of hundreds of mRNAs in dcp2Δ cells that appears to result directly from impaired decapping rather than elevated transcription. Interestingly, only a subset of mRNAs requires Dhh1 for targeting by Dcp2, and also generally requires the other decapping activators Pat1, Edc3 or Scd6; whereas most of the remaining transcripts utilize NMD factors for Dcp2-mediated turnover. Neither inefficient translation initiation nor stalled elongation appears to be a major driver of Dhh1-enhanced mRNA degradation. Surprisingly, ribosome profiling revealed that dcp2Δ confers widespread changes in relative translational efficiencies (TEs) that generally favor well-translated mRNAs. Because ribosome biogenesis is reduced while capped mRNA abundance is increased by dcp2&Delta, we propose that an increased ratio of mRNA to ribosomes increases competition among mRNAs for limiting ribosomes to favor efficiently translated mRNAs in dcp2Δ cells. Interestingly, genes involved in respiration or utilization of alternative carbon or nitrogen sources are up-regulated, and both mitochondrial function and cell filamentation are elevated in dcp2Δ cells, suggesting that decapping sculpts gene expression post-transcriptionally to fine-tune metabolic pathways and morphological transitions according to nutrient availability.

Data availability

Sequencing data have been deposited in GEO under accession codes GSE220578. All other data generated or analysed during this study are included in the manuscript and supporting files; Source Data files have been provided for all figures.

The following data sets were generated

1. Vijjamarri AK
2. Niu X
3. Vandermeulen MD
4. Onu C
5. Zhang F
6. Qiu H
7. Gupta N
8. Gaikwad S
9. Greenberg ML
10. Cullen PJ
11. Lin Z
12. Hinnebusch AG
(2023) Decapping factor Dcp2 controls mRNA abundance and translation to adjust metabolism and filamentation to nutrient availability.
NCBI Gene Expression Omnibus, GSE220578.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE220578
1. Vijjamarri AK
2. Niu X
3. Vandermeulen MD
4. Onu C
5. Zhang F
6. Qiu H
7. Gupta N
8. Gaikwad S
9. Greenberg ML
10. Cullen PJ
11. Lin Z
12. Hinnebusch AG
(2023) Decapping factor Dcp2 controls mRNA abundance and translation to adjust metabolism and filamentation to nutrient availability.
NCBI Gene Expression Omnibus, GSE216831.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE216831

The following previously published data sets were used

(2016) Ribosome profiling of dhh1∆ yeast
NCBI Gene Expression Omnibus, GSE87892.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE87892
(2016) Ribosome profiling study of Dhh1p overexpression and the dhh1 knockout strain using monosome-protected footprints
NCBI Gene Expression Omnibus, GSE81269.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE81269
1. He F
2. Celik A
3. Wu C
4. Jacobson 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
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
1. Zeidan Q
2. He F
3. Zhang F
4. Zhang H et al
(2019) Conserved mRNA-granule component Scd6 targets Dhh1 to repress translation initiation and activates Dcp2-mediated mRNA decay in vivo
NCBI Gene Expression Omnibus, GSE114892.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE114892

Article and author information

Author details

Anil Kumar Vijjamarri

Division of Molecular and Cellular Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, United States

Competing interests
No competing interests declared.
Xiao Niu

Department of Biology, Saint Louis University, Saint Louis, United States

Competing interests
No competing interests declared.
Matthew D Vandermeulen

Department of Biological Sciences, State University of New York, Buffalo, United States

Competing interests
No competing interests declared.
Chisom Onu

Department of Biological Sciences, Wayne State University, Detroit, United States

Competing interests
No competing interests declared.

"This ORCID iD identifies the author of this article:" 0000-0002-3338-5141
Fan Zhang

Division of Molecular and Cellular Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, United States

Competing interests
No competing interests declared.
Hongfang Qiu

Division of Molecular and Cellular Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, United States

Competing interests
No competing interests declared.
Neha Gupta

Division of Molecular and Cellular Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, United States

Competing interests
No competing interests declared.
Swati Gaikwad

Division of Molecular and Cellular Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, United States

Competing interests
No competing interests declared.

"This ORCID iD identifies the author of this article:" 0000-0002-1438-9497
Miriam L Greenberg

Department of Biological Sciences, Wayne State University, Detroit, United States

Competing interests
No competing interests declared.
Paul J Cullen

Department of Biological Sciences, State University of New York, Buffalo, United States

Competing interests
No competing interests declared.
Zhenguo Lin

Department of Biological Sciences, Saint Louis University, Saint Louis, United States

Competing interests
No competing interests declared.
Alan G Hinnebusch

Division of Molecular and Cellular Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, United States

For correspondence
ahinnebusch@nih.gov

Competing interests
Alan G Hinnebusch, Reviewing editor, eLife.

"This ORCID iD identifies the author of this article:" 0000-0002-1627-8395

Funding

National Heart, Lung, and Blood Institute (HL117880)

Miriam L Greenberg

National Heart, Lung, and Blood Institute (HL117880)

Chisom Onu

National Institute of General Medical Sciences (GM098629)

Matthew D Vandermeulen

National Institute of General Medical Sciences (GM098629)

Paul J Cullen

National Science Foundation (1951332)

Xiao Niu

National Science Foundation (1951332)

Zhenguo Lin

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.