The Francis Crick Institute, London, United Kingdom
Zornitsa Manova
The Francis Crick Institute, London, United Kingdom
Enrica Calvani
The Francis Crick Institute, London, United Kingdom
Alice Rossi
The Francis Crick Institute, London, United Kingdom
Raghu R Edupuganti
Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences (RIMLS), Oncode Institute, Radboud University Nijmegen, Nijmegen, Netherlands; Department of Human Genetics, University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, Biomedical Research Building, Miami, United States
Imke Ensinck
The Francis Crick Institute, London, United Kingdom
The Francis Crick Institute, London, United Kingdom
Harshil Patel
The Francis Crick Institute, London, United Kingdom
Joanna Kirkpatrick
The Francis Crick Institute, London, United Kingdom
Peter Faull
The Francis Crick Institute, London, United Kingdom; Biological Mass Spectrometry Facility, The University of Texas at Austin, Austin, United States
Ambrosius P Snijders
The Francis Crick Institute, London, United Kingdom
Michiel Vermeulen
Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences (RIMLS), Oncode Institute, Radboud University Nijmegen, Nijmegen, Netherlands
Markus Ralser
The Francis Crick Institute, London, United Kingdom; Department of Biochemistry, Charité Universitätsmedizin Berlin, Berlin, Germany
The Francis Crick Institute, London, United Kingdom; Dementia Research Institute, King's College London, London, United Kingdom
Nicholas M Luscombe
The Francis Crick Institute, London, United Kingdom; Department of Genetics, Evolution and Environment, UCL Genetics Institute, London, United Kingdom; Okinawa Institute of Science and Technology Graduate University, Okinawa, Japan
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.
