The RNA Methyltransferase Complex of WTAP, METTL3, and METTL14 Regulates Mitotic Clonal Expansion in Adipogenesis
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Le résumé fourni par la source
Adipocyte differentiation is regulated by various mechanisms, of which mitotic clonal expansion (MCE) is a key step. Although this process is known to be regulated by cell cycle modulators, the precise mechanism remains unclear. N6-Methyladenosine (m6A) posttranscriptional RNA modification, whose methylation and demethylation are performed by respective enzyme molecules, has recently been suggested to be involved in the regulation of adipogenesis. Here, we show that an RNA N6-adenosine methyltransferase complex consisting of Wilms' tumor 1-associating protein (WTAP), methyltransferase like 3 (METTL3), and METTL14 positively controls adipogenesis by promoting cell cycle transition in MCE during adipogenesis. WTAP, coupled with METTL3 and METTL14, is increased and distributed in nucleus by the induction of adipogenesis dependently on RNA in vitro. Knockdown of each of these three proteins leads to cell cycle arrest and impaired adipogenesis associated with suppression of cyclin A2 upregulation during MCE, whose knockdown also impairs adipogenesis. Consistent with this, Wtap heterozygous knockout mice are protected from diet-induced obesity with smaller size and number of adipocytes, leading to improved insulin sensitivity. These data provide a mechanism for adipogenesis through the WTAP-METTL3-METTL14 complex and a potential strategy for treatment of obesity and associated disorders.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- The RNA Methyltransferase Complex of WTAP, METTL3, and METTL14 Regulates Mitotic Clonal Expansion in Adipogenesis
- Date Crossref
- 01/08/2018
- Éditeur
- Informa UK Limited
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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The University of Tokyo Translational Systems Biology and Medicine Initiative (TSBMI) pays non établi dans la noticeUniversité ou école supérieure
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National Center for Global Health and Medicine pays non établi dans la noticeÉtablissement de santé
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Center for Global Health pays non établi dans la noticeOrganisme public
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Systems Biology Institute pays non établi dans la noticeOrganisation à but non lucratif
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Otsuma Women's University Department of Home Economics pays non établi dans la noticeUniversité ou école supérieure
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University of Toyama First Department of Internal Medicine pays non établi dans la noticeUniversité ou école supérieure
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Graduate School of Medicine Department of Diabetes and Metabolic Diseases pays non établi dans la noticeUniversité ou école supérieure
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Research Institute Department of Molecular Diabetic Medicine pays non établi dans la noticeStructure de recherche
Translational Systems Biology and Medicine Initiative (TSBMI) — The University of Tokyo, National Center for Global Health and Medicine et Center for Global Health, avec 5 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.