Saccharomyces Cerevisiae Modulates Cell Growth via Alternative Polyadenylation

Dynamic 3' UTRs variation mediated by APA is one of the major determinants of post-transcriptional regulation. Though some progress has been made in understanding its function in mammalian cells, the role of APA in the model organism S. cerevisiae, which lack of miRNAs, is a matter of debate. Unlike mammalian cells, most of S. cerevisiae genes tend to express mRNAs with longer 3′ UTRs in proliferating cells. Further analysis demonstrated that 3' UTRs length and mRNA expression were negatively correlated in different growth conditions. By combining APA sequencing and polysome profiling, we observed that mRNA isoforms with shorter 3' UTRs with a higher translational efficiency in proliferating cells but not quiescent. Further analysis demonstrated that different function genes translational efficiency control by APA are differential modulated and closely related with growth conditions. Furthermore, we observed the correlation between asRNAs and translational efficiency of different length 3′ UTR transcripts, suggests asRNAs may involve in the regulation of translational efficiency mediated by APA. Thus, this study indicates conservation of molecular function of APA in different Eukaryotes, highlighting the importance of APA in regulating gene function.由可变多聚腺苷酸化（APA）介导的动态3'非翻译区（3' UTR）变异是转录后调控的核心决定因素之一。尽管学界在解析其在哺乳动物细胞中的功能方面已取得一定进展，但针对缺乏微小RNA（miRNAs）的模式生物酿酒酵母（S. cerevisiae）中APA的生物学功能，目前仍存在学术争议。与哺乳动物细胞不同，多数酿酒酵母基因在增殖状态下倾向于表达携带更长3' UTR的信使RNA（mRNA）。进一步分析显示，在不同生长条件下，3' UTR长度与mRNA表达量呈显著负相关关系。本研究结合APA测序与多聚核糖体谱分析（polysome profiling），观察到在增殖细胞中，携带较短3' UTR的mRNA异构体具有更高的翻译效率，而该现象在静止期细胞中并未出现。后续分析进一步证实，受APA调控翻译效率的不同功能基因，其调控模式存在差异，且与细胞生长状态紧密相关。此外，我们还发现反义RNA（asRNAs）与不同长度3' UTR转录本的翻译效率之间存在显著关联，这提示asRNAs可能参与了APA介导的翻译效率调控通路。综上，本研究表明APA的分子功能在不同真核生物（Eukaryotes）中具有保守性，凸显了APA在调控基因功能中的关键意义。