RT Journal Article
SR Electronic
T1 m6A reader Pho92 is recruited co-transcriptionally and couples translation efficacy to mRNA decay to promote meiotic fitness in yeast
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.01.20.477035
DO 10.1101/2022.01.20.477035
A1 Radhika A. Varier
A1 Theodora Sideri
A1 Charlotte Capitanchik
A1 Zornitsa Manova
A1 Enrica Calvani
A1 Alice Rossi
A1 Raghu R. Edupuganti
A1 Imke Ensinck
A1 Vincent W.C. Chan
A1 Harshil Patel
A1 Joanna Kirkpatrick
A1 Peter Faull
A1 Ambrosius P. Snijders
A1 Michiel Vermeulen
A1 Markus Ralser
A1 Jernej Ule
A1 Nicholas M. Luscombe
A1 Folkert J. van Werven
YR 2022
UL http://biorxiv.org/content/early/2022/04/04/2022.01.20.477035.abstract
AB 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.Competing Interest StatementThe authors have declared no competing interest.