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Jiao-Na Zhang, Rui-Ting Wang, Francesca-Gioia Klinger, Shun-Feng Cheng, Wei Shen, Xiao-Feng Sun. RNA m6A dynamic modification mediated by nucleus-localized FTO is involved in follicular reserve. Zoological Research. doi: 10.24272/j.issn.2095-8137.2023.236
Citation: Jiao-Na Zhang, Rui-Ting Wang, Francesca-Gioia Klinger, Shun-Feng Cheng, Wei Shen, Xiao-Feng Sun. RNA m6A dynamic modification mediated by nucleus-localized FTO is involved in follicular reserve. Zoological Research. doi: 10.24272/j.issn.2095-8137.2023.236

RNA m6A dynamic modification mediated by nucleus-localized FTO is involved in follicular reserve

doi: 10.24272/j.issn.2095-8137.2023.236
The datasets for this study can be found in GSA under CRA number CRA004744 (https://ngdc.cncb.ac.cn/gsub/submit/gsa/subCRA006622/finishedOverview.GSA=CRA004744), Science Data Bank databases (DOI: 10.57760/sciencedb.15465) and NCBI under PRJNA1067203 (http://www.ncbi.nlm.nih.gov/bioproject/1067203)
The authors declare that they have no competing interests.
All authors contributed to the study conception and design. J.N.Z. and R.T.W. conducted the experiments; F.G.K. and S.F.C. analyzed the data; W.S. and X.F.S. designed the experiments; X.F.S drafted the manuscript. All authors read and approved the final version of the manuscript.
Funds:  This work was supported by the Natural Science Foundation of Shandong Province, China (ZR2017MC033), National Key Research and Development Program of China (2023YFD1300504), and Taishan Scholar Construction Foundation of Shandong Province, China (ts20190946)
More Information
  • In eukaryotic organisms, the most common internal modification of messenger RNA (mRNA) is N6-methyladenosine (m6A). This modification can be dynamically and reversibly controlled by specific enzymes known as m6A writers and erasers. The fat-mass and obesity-associated protein (FTO) catalyzes RNA demethylation and plays a critical role in various physiological and pathological processes. Our research identified dynamic alterations in both m6A and FTO during the assembly of primordial follicles, with an inverse relationship observed for m6A levels and nuclear-localized FTO expression. Application of Fto small interfering RNA (siRNA) altered the expression of genes related to cell proliferation, hormone regulation, and cell chemotaxis, and affected RNA alternative splicing. Overexpression of the full-length Fto gene led to changes in m6A levels, alternative splicing of Cdk5, cell proliferation, cell cycle progression, and proportion of primordial follicles. Conversely, overexpression of Fto lacking a nuclear localization signal (NLS) did not significantly alter m6A levels or primordial follicle assembly. These findings suggest that FTO, localized in the nucleus but not in the cytoplasm, regulates RNA m6A demethylation and plays a role in cell proliferation, cell cycle progression, and primordial follicle assembly. These results highlight the potential of m6A and its eraser FTO as possible biomarkers and therapeutic targets.
  • The datasets for this study can be found in GSA under CRA number CRA004744 (https://ngdc.cncb.ac.cn/gsub/submit/gsa/subCRA006622/finishedOverview.GSA=CRA004744), Science Data Bank databases (DOI: 10.57760/sciencedb.15465) and NCBI under PRJNA1067203 (http://www.ncbi.nlm.nih.gov/bioproject/1067203)
    The authors declare that they have no competing interests.
    All authors contributed to the study conception and design. J.N.Z. and R.T.W. conducted the experiments; F.G.K. and S.F.C. analyzed the data; W.S. and X.F.S. designed the experiments; X.F.S drafted the manuscript. All authors read and approved the final version of the manuscript.
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