N6-methyladenosine (m6A) reader Pho92 is recruited co-transcriptionally and couples translation to mRNA decay to promote meiotic fitness in yeast
- The Francis Crick Institute, United Kingdom
- Radboud University Nijmegen, Netherlands
Abstract
N6-methyladenosine (m6A) RNA modification impacts mRNA fate primarily via reader proteins, which dictate processes in development, stress, and disease. Yet little is known about m6A function in Saccharomyces cerevisiae, which occurs solely during early meiosis. Here we perform a multifaceted analysis of the m6A reader protein Pho92/Mrb1. Cross-linking immunoprecipitation analysis reveals that Pho92 associates with the 3’end of meiotic mRNAs in both an m6A-dependent and independent manner. Within cells, Pho92 transitions from the nucleus to the cytoplasm, and associates with translating ribosomes. In the nucleus Pho92 associates with target loci through its interaction with transcriptional elongator Paf1C. Functionally, we show that Pho92 promotes and links protein synthesis to mRNA decay. As such, the Pho92-mediated m6A-mRNA decay is contingent on active translation and the CCR4-NOT complex. We propose that the m6A reader Pho92 is loaded co-transcriptionally to facilitate protein synthesis and subsequent decay of m6A modified transcripts, and thereby promotes meiosis.
Data availability
The miCLIP, iCLIP and RNA-seq RAW and processed data are available to review GEO accession GSE193561:https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE193561
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High-resolution view of the yeast meiotic program revealed by ribosome profilingNCBI Gene Expression Omnibus, GSE34082.
Article and author information
Author details
Folkert Jacobus van Werven
Funding
Wellcome Trust (FC001203)
- Radhika A Varier
- Theodora Sideri
- Zornitsa Manova
- Alice Rossi
- Imke Ensinck
- Folkert Jacobus van Werven
Cancer Research UK (FC001203)
- Radhika A Varier
- Theodora Sideri
- Zornitsa Manova
- Alice Rossi
- Imke Ensinck
- Folkert Jacobus van Werven
Medical Research Council (FC001203)
- Radhika A Varier
- Theodora Sideri
- Zornitsa Manova
- Alice Rossi
- Imke Ensinck
- Folkert Jacobus van Werven
Wellcome Trust (FC010110)
- Charlotte Capitanchik
- Nicholas M Luscombe
Cancer Research UK (FC010110)
- Charlotte Capitanchik
- Nicholas M Luscombe
Medical Research Council (FC010110)
- Charlotte Capitanchik
- Nicholas M Luscombe
Medical Research Council (FC001134)
- Enrica Calvani Enrica.Calvani
- Markus Ralser
Cancer Research UK (FC001134)
- Enrica Calvani Enrica.Calvani
- Markus Ralser
Dutch Cancer Society
- Raghu R Edupuganti
- Michiel Vermeulen
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Timothy W Nilsen, Case Western Reserve University, United States
Version history
- Preprint posted: January 21, 2022 (view preprint)
- Received: October 7, 2022
- Accepted: November 13, 2022
- Accepted Manuscript published: November 24, 2022 (version 1)
- Accepted Manuscript updated: November 28, 2022 (version 2)
- Version of Record published: December 8, 2022 (version 3)
Copyright
© 2022, Varier 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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N6-methyladenosine (m6A) reader Pho92 is recruited co-transcriptionally and couples translation to mRNA decay to promote meiotic fitness in yeast
eLife 11:e84034.
https://doi.org/10.7554/eLife.84034
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