2020 Fiscal Year Annual Research Report
Translation control of circadian rhythms
| Project/Area Number |
18K14755
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| Research Institution | Osaka University |
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Principal Investigator |
MILLIUS ARTHUR 大阪大学, 免疫学フロンティア研究センター, 特任研究員(常勤) (80624858)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | Circadian rhythms / Translation / Ribosomal profiling / RNA structure / Regnase / uORF / Period2 / Machine learning |
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| Outline of Annual Research Achievements |
Defects in circadian rhythms are related to health problems, such as obesity, cancer, and depression, and understanding how RNA translation is regulated is important for developing new treatments. We used ribosome profiling to understand RNA translation in liver over a 24-h period and found that ribosomes bound to upstream open reading frames (uORFs) in circadian mRNAs repress mRNA translation. Mutation of the uORF in Per2 significantly reduced sleep in mutant mice compared to that of wild-type littermates. In the Akira lab, we used ribosome profiling to understand translation in wild-type and Regnase mutant hepatocytes, and in the Standley lab, we used RNA structure folding and machine learning to predict candidate Regnase target mRNAs.
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