Publicly Offered Research
Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
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.
27年度が最終年度であるため、記入しない。
All 2015 2014
All Journal Article (1 results) (of which Peer Reviewed: 1 results, Open Access: 1 results) Presentation (7 results) (of which Invited: 6 results)
J Clin Endocrinol Metab
Volume: 99 Issue: 2 Pages: 257-62
10.1210/jc.2013-3279
