細胞内メチレーションリズムと時計遺伝子mRNA制御のクロストークの分子基盤
Publicly Offered Research
| Project Area | Crosstalk of transcriptional control and energy pathways by hub metabolites |
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| Project/Area Number |
26116713
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| Research Category |
Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Kyoto University |
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Principal Investigator |
FUSTIN JM 京都大学, 薬学研究科(研究院), 講師 (50711818)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
Fiscal Year 2015: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2014: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
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| Keywords | m6A methylation / Circadian / RNA methylation |
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| Outline of Annual Research Achievements |
In the past year we have made good progress in our investigations, and are currently preparing our new manuscript.
We have quantified m6A mRNA methylation every 4 hours during 24 hours and have identified significant methylation peaks. A significant portion of these peaks were detected at all time points but some peaks were detected in a fraction of the samples. Interestingly, we have also observed significant circadian variations in the amount of m6A peaks detected as well as in the coverage of common peaks, with significantly higher methylation during the day.
We have also focussed our investigations on one candidate transcript characterised by one strongly significant peak detected at all time points. We have then investigated the role of this m6A site and identified that it controls the expression of two alternatively spliced mRNA of unknown function. We have then characterised at the proteomic level the function of these two isoforms and found that they have opposite functions on the circadian clock. To identify the physiological function of these two isoforms, we are currently making mice with a conditional deletion of only one of these isoforms.
In parallel we have also established mice with non-coding deletions of the m6A methylated locus in the 3'-UTR of our candidate gene by CRISPR-Cas9-mediated genome editing. We are currently characterising these mice.
In parallel we are continuing the establishment of Mettl3 conditional knock-out mice to obtain liver- and SCN-specific KO. This is proceeding well.
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| Research Progress Status |
27年度が最終年度であるため、記入しない。
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| Strategy for Future Research Activity |
27年度が最終年度であるため、記入しない。
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Report
(2 results)
Research Products
(8 results)
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[Journal Article] Isoform-specific monoclonal antibodies against 3beta-hydroxysteroid dehy drogenase/isomerase family provide markers for subclassification of hum an primary aldosteronism. .2014
Author(s)
Doi M, Satoh F, Maekawa T, N akamura Y, Fustin JM, Tainaka M, Hotta Y, Takahashi Y, Morimoto R, Takase K, Ito S, Sasano H, and Okamura H
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Journal Title
J Clin Endocrinol Metab
Volume: 99
Issue: 2
Pages: 257-62
DOI
Related Report
Peer Reviewed / Open Access
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