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

Joseph V Geisberg, Zarmik Moqtaderi, Kevin Struhl

Proceedings of the National Academy of Sciences of the United States of America 2023 May 02

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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.

Citation

Joseph V Geisberg, Zarmik Moqtaderi, Kevin Struhl. Condition-specific 3' mRNA isoform half-lives and stability elements in yeast. Proceedings of the National Academy of Sciences of the United States of America. 2023 May 02;120(18):e2301117120