Transcriptome maps of general eukaryotic RNA degradation factors
- Max Planck Institute for Biophysical Chemistry, Germany
Abstract
RNA degradation pathways enable RNA processing, the regulation of RNA levels, and the surveillance of aberrant or poorly functional RNAs in cells. Here we provide transcriptome-wide RNA-binding profiles of 30 general RNA degradation factors in the yeast Saccharomyces cerevisiae. The profiles reveal the distribution of degradation factors between different RNA classes. They are consistent with the canonical degradation pathway for closed-loop forming mRNAs after deadenylation. Modeling based on mRNA half-lives suggests that most degradation factors bind intact mRNAs, whereas decapping factors are recruited only for mRNA degradation, consistent with decapping being a rate-limiting step. Decapping factors preferentially bind mRNAs with non-optimal codons, consistent with rapid degradation of inefficiently translated mRNAs. Global analysis suggests that the nuclear surveillance machinery, including the complexes Nrd1/Nab3 and TRAMP4, targets aberrant nuclear RNAs and processes snoRNAs.
Data availability
Sequencing data have been deposited in GEO under accession codes GSE 128312.
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Transcriptome maps of general eukaryotic RNA degradation factorsNCBI Gene Expression Omnibus, GSE8128312.
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Transcriptome maps of mRNP biogenesis factors define pre-mRNA recognitionNCBI Gene Expression Omnibus, GSE59676.
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Genome-wide analysis of RNA polymerase II termination at protein-coding genes.NCBI Gene Expression Omnibus, GSE79222.
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RNA-dependent chromatin association of transcription elongation factors and Pol II CTD kinasesNCBI Gene Expression Omnibus, GSE81822.
Article and author information
Author details
Salma Sohrabi-Jahromi
Katharina B Hofmann
Funding
European Research Council (Advanced Grant Transregulon)
- Patrick Cramer
Volkswagen Foundation
- Patrick Cramer
Deutsche Forschungsgemeinschaft (SPP1935 grant CR 117/6-1)
- Johannes Soeding
- Patrick Cramer
Max-Planck-Gesellschaft (Open-Access funding)
- Patrick Cramer
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Torben Heick Jensen, Aarhus University, Denmark
Version history
- Received: March 24, 2019
- Accepted: May 27, 2019
- Accepted Manuscript published: May 28, 2019 (version 1)
- Version of Record published: June 14, 2019 (version 2)
Copyright
© 2019, Sohrabi-Jahromi 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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Transcriptome maps of general eukaryotic RNA degradation factors
eLife 8:e47040.
https://doi.org/10.7554/eLife.47040
Further reading
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Recent findings indicate that the translation elongation rate influences mRNA stability. One of the factors that has been implicated in this link between mRNA decay and translation speed is the yeast DEAD-box helicase Dhh1p. Here, we demonstrated that the human ortholog of Dhh1p, DDX6, triggers the deadenylation-dependent decay of inefficiently translated mRNAs in human cells. DDX6 interacts with the ribosome through the Phe-Asp-Phe (FDF) motif in its RecA2 domain. Furthermore, RecA2-mediated interactions and ATPase activity are both required for DDX6 to destabilize inefficiently translated mRNAs. Using ribosome profiling and RNA sequencing, we identified two classes of endogenous mRNAs that are regulated in a DDX6-dependent manner. The identified targets are either translationally regulated or regulated at the steady-state-level and either exhibit signatures of poor overall translation or of locally reduced ribosome translocation rates. Transferring the identified sequence stretches into a reporter mRNA caused translation- and DDX6-dependent degradation of the reporter mRNA. In summary, these results identify DDX6 as a crucial regulator of mRNA translation and decay triggered by slow ribosome movement and provide insights into the mechanism by which DDX6 destabilizes inefficiently translated mRNAs.
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