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Condition-specific 3′ mRNA isoform half-lives and stability elements in yeast

Alternative polyadenylation generates numerous 3′ mRNA isoforms that can differ in their stability, structure, and function. These isoforms can be used to map mRNA stabilizing and destabilizing elements within 3′ untranslated regions (3′UTRs). Here, we examine how environmental conditions affect 3′...

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Autores principales: Geisberg, Joseph V., Moqtaderi, Zarmik, Struhl, Kevin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10161003/
https://www.ncbi.nlm.nih.gov/pubmed/37094136
http://dx.doi.org/10.1073/pnas.2301117120
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author Geisberg, Joseph V.
Moqtaderi, Zarmik
Struhl, Kevin
author_facet Geisberg, Joseph V.
Moqtaderi, Zarmik
Struhl, Kevin
author_sort Geisberg, Joseph V.
collection PubMed
description Alternative polyadenylation generates numerous 3′ mRNA isoforms that can differ in their stability, structure, and function. These isoforms can be used to map mRNA stabilizing and destabilizing elements within 3′ untranslated regions (3′UTRs). Here, we examine how environmental conditions affect 3′ mRNA isoform turnover and structure in yeast cells on a transcriptome scale. Isoform stability broadly increases when cells grow more slowly, with relative half-lives of most isoforms being well correlated across multiple conditions. Surprisingly, dimethyl sulfate probing reveals that individual 3′ isoforms have similar structures across different conditions, in contrast to the extensive structural differences that can exist between closely related isoforms in an individual condition. Unexpectedly, most mRNA stabilizing and destabilizing elements function only in a single growth condition. The genes associated with some classes of condition-specific stability elements are enriched for different functional categories, suggesting that regulated mRNA stability might contribute to adaptation to different growth environments. Condition-specific stability elements do not result in corresponding condition-specific changes in steady-state mRNA isoform levels. This observation is consistent with a compensatory mechanism between polyadenylation and stability, and it suggests that condition-specific mRNA stability elements might largely reflect condition-specific regulation of mRNA 3′ end formation.
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spelling pubmed-101610032023-10-24 Condition-specific 3′ mRNA isoform half-lives and stability elements in yeast Geisberg, Joseph V. Moqtaderi, Zarmik Struhl, Kevin Proc Natl Acad Sci U S A Biological Sciences Alternative polyadenylation generates numerous 3′ mRNA isoforms that can differ in their stability, structure, and function. These isoforms can be used to map mRNA stabilizing and destabilizing elements within 3′ untranslated regions (3′UTRs). Here, we examine how environmental conditions affect 3′ mRNA isoform turnover and structure in yeast cells on a transcriptome scale. Isoform stability broadly increases when cells grow more slowly, with relative half-lives of most isoforms being well correlated across multiple conditions. Surprisingly, dimethyl sulfate probing reveals that individual 3′ isoforms have similar structures across different conditions, in contrast to the extensive structural differences that can exist between closely related isoforms in an individual condition. Unexpectedly, most mRNA stabilizing and destabilizing elements function only in a single growth condition. The genes associated with some classes of condition-specific stability elements are enriched for different functional categories, suggesting that regulated mRNA stability might contribute to adaptation to different growth environments. Condition-specific stability elements do not result in corresponding condition-specific changes in steady-state mRNA isoform levels. This observation is consistent with a compensatory mechanism between polyadenylation and stability, and it suggests that condition-specific mRNA stability elements might largely reflect condition-specific regulation of mRNA 3′ end formation. National Academy of Sciences 2023-04-24 2023-05-02 /pmc/articles/PMC10161003/ /pubmed/37094136 http://dx.doi.org/10.1073/pnas.2301117120 Text en Copyright © 2023 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Biological Sciences
Geisberg, Joseph V.
Moqtaderi, Zarmik
Struhl, Kevin
Condition-specific 3′ mRNA isoform half-lives and stability elements in yeast
title Condition-specific 3′ mRNA isoform half-lives and stability elements in yeast
title_full Condition-specific 3′ mRNA isoform half-lives and stability elements in yeast
title_fullStr Condition-specific 3′ mRNA isoform half-lives and stability elements in yeast
title_full_unstemmed Condition-specific 3′ mRNA isoform half-lives and stability elements in yeast
title_short Condition-specific 3′ mRNA isoform half-lives and stability elements in yeast
title_sort condition-specific 3′ mrna isoform half-lives and stability elements in yeast
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10161003/
https://www.ncbi.nlm.nih.gov/pubmed/37094136
http://dx.doi.org/10.1073/pnas.2301117120
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