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Kar4 is Required for the Normal Pattern of Meiotic Gene Expression

Kar4p, the yeast homolog of the mammalian methyltransferase subunit METTL14, is required for the initiation of meiosis and has at least two distinct functions in regulating the meiotic program. Cells lacking Kar4p can be driven to sporulate by co-overexpressing the master meiotic transcription facto...

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Autores principales: Park, Zachory M., Remillard, Matthew, Rose, Mark D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9900936/
https://www.ncbi.nlm.nih.gov/pubmed/36747654
http://dx.doi.org/10.1101/2023.01.29.526097
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author Park, Zachory M.
Remillard, Matthew
Rose, Mark D.
author_facet Park, Zachory M.
Remillard, Matthew
Rose, Mark D.
author_sort Park, Zachory M.
collection PubMed
description Kar4p, the yeast homolog of the mammalian methyltransferase subunit METTL14, is required for the initiation of meiosis and has at least two distinct functions in regulating the meiotic program. Cells lacking Kar4p can be driven to sporulate by co-overexpressing the master meiotic transcription factor, IME1, and the translational regulator, RIM4, suggesting that Kar4p functions at both the transcriptional and translational level to regulate meiosis. Using microarray analysis and RNA sequencing, we found that kar4Δ/Δ mutants have a largely wild type transcriptional profile with the exception of two groups of genes that show delayed and reduced expression: (1) a set of Ime1p-dependent early genes as well as IME1, and (2) a set of late genes dependent on the mid-meiotic transcription factor, Ndt80p. The early gene expression defect is rescued by overexpressing IME1, but the late defect is only suppressed by overexpression of both IME1 and RIM4. Mass spectrometry analysis identified several genes involved in meiotic recombination with strongly reduced protein levels, but with little to no reduction in transcript levels in kar4Δ/Δ after IME1 overexpression. The low levels of these proteins were rescued by overexpression of RIM4 and IME1, but not by the overexpression of IME1 alone. These data expand our understanding of the role of Kar4p in regulating meiosis and provide key insights into a potential mechanism of Kar4p’s later meiotic function that is independent of mRNA methylation.
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spelling pubmed-99009362023-02-07 Kar4 is Required for the Normal Pattern of Meiotic Gene Expression Park, Zachory M. Remillard, Matthew Rose, Mark D. bioRxiv Article Kar4p, the yeast homolog of the mammalian methyltransferase subunit METTL14, is required for the initiation of meiosis and has at least two distinct functions in regulating the meiotic program. Cells lacking Kar4p can be driven to sporulate by co-overexpressing the master meiotic transcription factor, IME1, and the translational regulator, RIM4, suggesting that Kar4p functions at both the transcriptional and translational level to regulate meiosis. Using microarray analysis and RNA sequencing, we found that kar4Δ/Δ mutants have a largely wild type transcriptional profile with the exception of two groups of genes that show delayed and reduced expression: (1) a set of Ime1p-dependent early genes as well as IME1, and (2) a set of late genes dependent on the mid-meiotic transcription factor, Ndt80p. The early gene expression defect is rescued by overexpressing IME1, but the late defect is only suppressed by overexpression of both IME1 and RIM4. Mass spectrometry analysis identified several genes involved in meiotic recombination with strongly reduced protein levels, but with little to no reduction in transcript levels in kar4Δ/Δ after IME1 overexpression. The low levels of these proteins were rescued by overexpression of RIM4 and IME1, but not by the overexpression of IME1 alone. These data expand our understanding of the role of Kar4p in regulating meiosis and provide key insights into a potential mechanism of Kar4p’s later meiotic function that is independent of mRNA methylation. Cold Spring Harbor Laboratory 2023-01-29 /pmc/articles/PMC9900936/ /pubmed/36747654 http://dx.doi.org/10.1101/2023.01.29.526097 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
spellingShingle Article
Park, Zachory M.
Remillard, Matthew
Rose, Mark D.
Kar4 is Required for the Normal Pattern of Meiotic Gene Expression
title Kar4 is Required for the Normal Pattern of Meiotic Gene Expression
title_full Kar4 is Required for the Normal Pattern of Meiotic Gene Expression
title_fullStr Kar4 is Required for the Normal Pattern of Meiotic Gene Expression
title_full_unstemmed Kar4 is Required for the Normal Pattern of Meiotic Gene Expression
title_short Kar4 is Required for the Normal Pattern of Meiotic Gene Expression
title_sort kar4 is required for the normal pattern of meiotic gene expression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9900936/
https://www.ncbi.nlm.nih.gov/pubmed/36747654
http://dx.doi.org/10.1101/2023.01.29.526097
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