Using fission yeast to unravel polyadenylation control

几乎每一个真核生物的mRNA都有一个3'腺苷（A）尾。poly（A）的这种延伸在mRNA的生理学中起着关键作用，包括核输出，稳定性和翻译。然而，到目前为止，在从头合成过程中决定poly（A）尾长的分子机制仍然难以捉摸。这是一个重要的问题，因为如果没有这样的知识，详细了解poly（A）尾长如何控制mRNA代谢以及相应的基因调控是非常不可能的。所提出的研究的目的是确定聚（A）尾长控制被确定和调节的机制。我们的假设是，核poly（A）结合蛋白在poly（A）尾长的决定中起着关键作用。我们最近克隆和鉴定了裂殖酵母裂殖酵母中哺乳动物核多聚腺苷酸结合蛋白的功能同源物。因为有一个显着程度的保守，从酵母到哺乳动物之间的多聚腺苷酸化所需的组件，这些研究酵母使我们能够迅速获得适用于所有真核生物的实验见解。阐明核poly（A）结合蛋白调节mRNA聚腺苷酸化的机制，并更好地了解poly（A）尾长控制，预计从我们的研究计划。

Nearly every eukaryotic mRNA possesses a 3' adenosine (A) tail. This stretch of poly(A) plays key roles in the physiology of an mRNA, including nuclear export, stability, and translation. As yet, however, the molecular mechanism by which poly(A) tail length is determined during de novo synthesis remains elusive. This is an important problem, because without such knowledge a detailed understanding of how poly(A) tail length controls mRNA metabolism, and accordingly gene regulation, is highly unlikely. The objective of the proposed research is to determine the mechanism by which poly(A) tail length control is determined and regulated. It is our hypothesis that the nuclear poly(A) binding protein plays a critical role in the determination of poly(A) tail length. We have recently cloned and characterized a functional homolog of the mammalian nuclear poly(A)-binding protein in the fission yeast Schizosaccharomyces pombe. Because there is a significant degree of conservation from yeast to mammals among the components required for polyadenylation, these studies in yeast allow us to rapidly obtain experimental insights applicable to all eukaryotes. Elucidation of the mechanism by which the nuclear poly(A) binding protein regulates mRNA polyadenylation and a better understanding of poly(A) tail length control are anticipated from our research program.