RNA m6A dynamic modification mediated by nucleuslocalized FTO is involved in follicular reserve  

作　　者：Jiao-Na Zhang Rui-Ting Wang Francesca-Gioia Klinger Shun-Feng Cheng Wei Shen Xiao-Feng Sun 

机构地区：[1]College of Life Sciences,Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong,Qingdao Agricultural University,Qingdao,Shandong 266109,China [2]Department of Biomedicine and Prevention,University of Rome Tor Vergata,Rome 00133,Italy

出　　处：《Zoological Research》2024年第2期415-428,共14页动物学研究（英文）

基　　金：supported by the Natural Science Foundation of Shandong Province,China (ZR2017MC033);National Key Research and Development Program of China (2023YFD1300504);Taishan Scholar Construction Foundation of Shandong Province,China (ts20190946)。

摘　　要：In eukaryotic organisms,the most common internal modification of messenger RNA(m RNA)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(si RNA)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.

关 键 词：m6A FTO OVARY Primordial follicle assembly Alternative splicing 

分 类 号：Q75[生物学—分子生物学]