The fission yeast S. pombe, like S. cerevisiae, has a highly regulated gene expression program for meiosis. However, it appears that a significant portion of the meiotic regulation is not at the transcriptional level, but rather post-transcriptional, at the level of RNA processing. S. pombe has a sophisticated apparatus for RNA processing, including regulation of splicing, and including RNAi. Here, we will focus on these RNA-mediated mechanisms of meiotic regulation, to complement investigations of transcription-factor based regulation in S. cerevisiae. We will provide a detailed characterization of the meiotic transcriptome. We will investigate the inter-related effects of 3'end processing (e.g., cleavage and polyadenylation), RNA turnover, and RNA splicing, and how these processes and the Mmil protein combine to express the early meiotic genes. We will investigate the roles of the anti-sense transcripts found over many of the middle meiotic genes. Finally, in collaboration with Drs. Futcher, Neiman, and Sternglanz we will identify the RNA targets of a number of important meiotic RNA binding proteins in both S. pombe and S. cerevisiae.
This study has relevance to human disease in several aspects. First, mutations affecting splicing are implicated in a majority of human diseases and fission yeast offers one of the two simplest model systems for studies of splicing regulation with arguably greater similarity to human than budding yeast. Second, basic understanding of meiosis is helpful in understanding infertility and birth defects. Finally, the meiotic cycle is a special variation of the vegetative cell cycle and thus will further understanding of carcinogenesis.
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