m6A reader Pho92 is recruited co-transcriptionally and couples translation efficacy to mRNA decay to promote meiotic fitness in yeast

Jernej Ule; Rhadika A. Varier; Theodora Sideri; Charlotte Capitanchik; Zornitsa Manova; Enrica Calvani; Alice Rossi; Raghu Edupuganti; Imke Ensinck; Vincent W.C Chan; Harshil Patel; Joanne Kirkpatrick; Peter A. Faull; Ambrosius P. Snijders; Michael Vermeulen; Markus Ralser; Nicholas M. Luscombe; Folkert J. van Werven

doi:10.1101/2022.01.20.477035;

m6A reader Pho92 is recruited co-transcriptionally and couples translation efficacy to mRNA decay to promote meiotic fitness in yeast

Jernej Ule, Rhadika A. Varier, Theodora Sideri, Charlotte Capitanchik, Zornitsa Manova, Enrica Calvani, Alice Rossi, Raghu Edupuganti, Imke Ensinck, Vincent W.C Chan, Harshil Patel, Joanne Kirkpatrick, Peter A. Faull, Ambrosius P. Snijders, Michael Vermeulen, Markus Ralser, Nicholas M. Luscombe, Folkert J. van Werven

Research output: Working paper/Preprint › Preprint

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 prime 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 correct translation and subsequent decay of m6A modified transcripts, and thereby promotes meiosis.

Original language	English
Publisher	Cold Spring Harbor Laboratory Press
DOIs	https://doi.org/10.1101/2022.01.20.477035;
Publication status	Published - 1 Jan 2022

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Ule, J., Varier, R. A., Sideri, T., Capitanchik, C., Manova, Z., Calvani, E., Rossi, A., Edupuganti, R., Ensinck, I., Chan, V. W. C., Patel, H., Kirkpatrick, J., Faull, P. A., Snijders, A. P., Vermeulen, M., Ralser, M., Luscombe, N. M., & van Werven, F. J. (2022). m6A reader Pho92 is recruited co-transcriptionally and couples translation efficacy to mRNA decay to promote meiotic fitness in yeast. Cold Spring Harbor Laboratory Press. https://doi.org/10.1101/2022.01.20.477035;

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title = "m6A reader Pho92 is recruited co-transcriptionally and couples translation efficacy to mRNA decay to promote meiotic fitness in yeast",

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 prime 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 correct translation and subsequent decay of m6A modified transcripts, and thereby promotes meiosis.",

author = "Jernej Ule and Varier, {Rhadika A.} and Theodora Sideri and Charlotte Capitanchik and Zornitsa Manova and Enrica Calvani and Alice Rossi and Raghu Edupuganti and Imke Ensinck and Chan, {Vincent W.C} and Harshil Patel and Joanne Kirkpatrick and Faull, {Peter A.} and Snijders, {Ambrosius P.} and Michael Vermeulen and Markus Ralser and Luscombe, {Nicholas M.} and {van Werven}, {Folkert J.}",

year = "2022",

month = jan,

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doi = "10.1101/2022.01.20.477035;",

language = "English",

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Ule, J, Varier, RA, Sideri, T, Capitanchik, C, Manova, Z, Calvani, E, Rossi, A, Edupuganti, R, Ensinck, I, Chan, VWC, Patel, H, Kirkpatrick, J, Faull, PA, Snijders, AP, Vermeulen, M, Ralser, M, Luscombe, NM & van Werven, FJ 2022 'm6A reader Pho92 is recruited co-transcriptionally and couples translation efficacy to mRNA decay to promote meiotic fitness in yeast' Cold Spring Harbor Laboratory Press. https://doi.org/10.1101/2022.01.20.477035;

TY - UNPB

T1 - m6A reader Pho92 is recruited co-transcriptionally and couples translation efficacy to mRNA decay to promote meiotic fitness in yeast

AU - Ule, Jernej

AU - Varier, Rhadika A.

AU - Sideri, Theodora

AU - Capitanchik, Charlotte

AU - Manova, Zornitsa

AU - Calvani, Enrica

AU - Rossi, Alice

AU - Edupuganti, Raghu

AU - Ensinck, Imke

AU - Chan, Vincent W.C

AU - Patel, Harshil

AU - Kirkpatrick, Joanne

AU - Faull, Peter A.

AU - Snijders, Ambrosius P.

AU - Vermeulen, Michael

AU - Ralser, Markus

AU - Luscombe, Nicholas M.

AU - van Werven, Folkert J.

PY - 2022/1/1

Y1 - 2022/1/1

N2 - 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 prime 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 correct translation and subsequent decay of m6A modified transcripts, and thereby promotes meiosis.

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 prime 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 correct translation and subsequent decay of m6A modified transcripts, and thereby promotes meiosis.

U2 - 10.1101/2022.01.20.477035;

DO - 10.1101/2022.01.20.477035;

M3 - Preprint

BT - m6A reader Pho92 is recruited co-transcriptionally and couples translation efficacy to mRNA decay to promote meiotic fitness in yeast

PB - Cold Spring Harbor Laboratory Press

ER -

m6A reader Pho92 is recruited co-transcriptionally and couples translation efficacy to mRNA decay to promote meiotic fitness in yeast

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