| First Author | Zhang X | Year | 2022 |
| Journal | Nat Commun | Volume | 13 |
| Issue | 1 | Pages | 7038 |
| PubMed ID | 36396934 | Mgi Jnum | J:334205 |
| Mgi Id | MGI:7387662 | Doi | 10.1038/s41467-022-34808-2 |
| Citation | Zhang X, et al. (2022) N6-methyladenosine modification governs liver glycogenesis by stabilizing the glycogen synthase 2 mRNA. Nat Commun 13(1):7038 |
| abstractText | Hepatic glycogen is the main source of blood glucose and controls the intervals between meals in mammals. Hepatic glycogen storage in mammalian pups is insufficient compared to their adult counterparts; however, the detailed molecular mechanism is poorly understood. Here, we show that, similar to glycogen storage pattern, N6-methyladenosine (m6A) modification in mRNAs gradually increases during the growth of mice in liver. Strikingly, in the hepatocyte-specific Mettl3 knockout mice, loss of m6A modification disrupts liver glycogen storage. On the mechanism, mRNA of Gys2, the liver-specific glycogen synthase, is a substrate of METTL3 and plays a critical role in m6A-mediated glycogenesis. Furthermore, IGF2BP2, a "reader" protein of m6A, stabilizes the mRNA of Gys2. More importantly, reconstitution of GYS2 almost rescues liver glycogenesis in Mettl3-cKO mice. Collectively, a METTL3-IGF2BP2-GYS2 axis, in which METTL3 and IGF2BP2 regulate glycogenesis as "writer" and "reader" proteins respectively, is essential on maintenance of liver glycogenesis in mammals. |
