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’ 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.可变聚腺苷酸化（Alternative polyadenylation）可产生众多3’ mRNA异构体，这些异构体在稳定性、结构与功能上存在差异。此类异构体可用于定位3’非翻译区（3’ untranslated regions, 3’UTRs）内的mRNA稳定元件与去稳定元件。本研究探究了环境条件如何在转录组尺度上影响酵母细胞内3’ mRNA异构体的周转与结构。当细胞生长速率放缓时，异构体的稳定性整体升高，多数异构体的相对半衰期在多种实验条件下呈现良好的相关性。令人意外的是，硫酸二甲酯（dimethyl sulfate）探测结果显示，不同条件下的单个3’异构体结构相似，这与单一条件下密切相关异构体间广泛存在的结构差异形成鲜明对比。出乎意料的是，多数mRNA稳定元件与去稳定元件仅在单一生长条件下发挥功能。部分条件特异性稳定性元件所关联的基因富集于不同的功能类别，这提示受调控的mRNA稳定性可能有助于细胞适应不同的生长环境。条件特异性稳定性元件并未导致稳态mRNA异构体水平出现相应的条件特异性变化。这一观察结果与聚腺苷酸化与稳定性之间的补偿机制相符，同时表明条件特异性mRNA稳定性元件可能在很大程度上反映了mRNA 3’端形成的条件特异性调控。