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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Program Projects (P01)
Project #
5P01GM088297-03
Application #
8375742
Study Section
Special Emphasis Panel (ZRG1-CB-Q)
Project Start
Project End
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
3
Fiscal Year
2012
Total Cost
$339,037
Indirect Cost
$120,731
Name
State University New York Stony Brook
Department
Type
DUNS #
804878247
City
Stony Brook
State
NY
Country
United States
Zip Code
11794
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Jin, Liang; Neiman, Aaron M (2016) Post-transcriptional regulation in budding yeast meiosis. Curr Genet 62:313-5
Chen, Xiangyu; Suhandynata, Ray T; Sandhu, Rima et al. (2015) Phosphorylation of the Synaptonemal Complex Protein Zip1 Regulates the Crossover/Noncrossover Decision during Yeast Meiosis. PLoS Biol 13:e1002329
Jin, Liang; Zhang, Kai; Xu, Yifeng et al. (2015) Sequestration of mRNAs Modulates the Timing of Translation during Meiosis in Budding Yeast. Mol Cell Biol 35:3448-58
Lin, Ching-Jung; Smibert, Peter; Zhao, Xiaoyu et al. (2015) An extensive allelic series of Drosophila kae1 mutants reveals diverse and tissue-specific requirements for t6A biogenesis. RNA 21:2103-18
Garg, Angad; Futcher, Bruce; Leatherwood, Janet (2015) A new transcription factor for mitosis: in Schizosaccharomyces pombe, the RFX transcription factor Sak1 works with forkhead factors to regulate mitotic expression. Nucleic Acids Res 43:6874-88
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Lo, Hsiao-Chi; Kunz, Ryan C; Chen, Xiangyu et al. (2012) Cdc7-Dbf4 is a gene-specific regulator of meiotic transcription in yeast. Mol Cell Biol 32:541-57
Yuan, Hua; Rossetto, Dorine; Mellert, Hestia et al. (2012) MYST protein acetyltransferase activity requires active site lysine autoacetylation. EMBO J 31:58-70

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