Using fission yeast to unravel polyadenylation control

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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.