Using fission yeast to unravel polyadenylation-dependent gene regulation

信使RNA(信使RNA)是编码细胞蛋白质的基本分子。因为合成和衰退之间的平衡决定了mRNA的稳定丰度，所以RNA降解成为基因调控的一个组成部分。在mRNA3‘端是一段多聚腺苷(A)，通常通过促进稳定性和胞质翻译来刺激基因表达。与mRNA聚腺苷酸化的这种典型作用相反，3‘端的聚(A)尾也可以代表一条破坏RNA的途径。我们的研究计划集中在了解聚腺苷酸化控制裂解酵母(Schizosaccharmyces Pombe)中mRNA稳定性的机制。因此，我们最近发现了一个依赖于多聚腺苷化的mRNA降解系统，它依赖于一种名为Mmi1的蛋白质，并在有丝分裂细胞周期中选择性地降解减数分裂转录产物。这项建议的目的是确定多聚腺苷控制分裂酵母减数分裂基因表达的机制，这是追求这一研究计划长期目标的一步。提出了以下具体目标：

Messenger RNAs (mRNA) are the fundamental molecules responsible for encoding cellular proteins. Because the balance between synthesis and decay determines the steady-state abundance of an mRNA, RNA degradation becomes an integral part of gene regulation. On the mRNA 3' end is a stretch of polyadenosine (A) that normally stimulates gene expression by promoting stability and cytosolic translation. Contrasting this canonical role of mRNA polyadenylation, the 3' end poly(A) tail can also represent a path to RNA destruction. Our research program is centered on understanding mechanisms by which polyadenylation controls mRNA stability in the fission yeast, Schizosaccharomyces pombe. Accordingly, we have recently discovered a polyadenylation-dependent mRNA degradation system that depends on a protein named, Mmi1, and that selectively degrades meiotic transcripts during the mitotic cell cycle. The objective of this proposal, which is a step in the pursuit of the long-term goal of this research program, is to determine the mechanism by which polyadenylation controls meiotic gene expression in fission yeast. The following specific aims are proposed: