Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115.
Proc Natl Acad Sci U S A. 2023 May 2;120(18):e2301117120. doi: 10.1073/pnas.2301117120. Epub 2023 Apr 24.
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.
可变 polyadenylation 会生成许多在稳定性、结构和功能上存在差异的 3' mRNA 异构体。这些异构体可用于在 3'非翻译区(3'UTR)内定位 mRNA 稳定和不稳定元件。在这里,我们在转录组范围内研究了环境条件如何影响酵母细胞中 3' mRNA 异构体的周转率和结构。当细胞生长缓慢时,异构体的稳定性会广泛增加,大多数异构体的相对半衰期在多种条件下都很好地相关。令人惊讶的是,二甲基硫酸盐探测显示,与个体条件下密切相关的异构体之间可能存在的广泛结构差异相比,单个 3' 异构体在不同条件下具有相似的结构。出乎意料的是,大多数 mRNA 稳定和不稳定元件仅在单个生长条件下起作用。与一些特定条件稳定性元件相关的基因富集了不同的功能类别,这表明受调控的 mRNA 稳定性可能有助于适应不同的生长环境。特定条件的稳定性元件不会导致稳态 mRNA 异构体水平出现相应的特定条件变化。这一观察结果与 polyadenylation 和稳定性之间的补偿机制一致,这表明特定条件的 mRNA 稳定性元件可能在很大程度上反映了 3' 端形成的特定条件调节。