| First Author | Ignatova VV | Year | 2020 |
| Journal | Genes Dev | Volume | 34 |
| Issue | 9-10 | Pages | 715-729 |
| PubMed ID | 32217665 | Mgi Jnum | J:289086 |
| Mgi Id | MGI:6436417 | Doi | 10.1101/gad.333369.119 |
| Citation | Ignatova VV, et al. (2020) The rRNA m(6)A methyltransferase METTL5 is involved in pluripotency and developmental programs. Genes Dev 34(9-10):715-729 |
| abstractText | Covalent chemical modifications of cellular RNAs directly impact all biological processes. However, our mechanistic understanding of the enzymes catalyzing these modifications, their substrates and biological functions, remains vague. Amongst RNA modifications N(6)-methyladenosine (m(6)A) is widespread and found in messenger (mRNA), ribosomal (rRNA), and noncoding RNAs. Here, we undertook a systematic screen to uncover new RNA methyltransferases. We demonstrate that the methyltransferase-like 5 (METTL5) protein catalyzes m(6)A in 18S rRNA at position A1832 We report that absence of Mettl5 in mouse embryonic stem cells (mESCs) results in a decrease in global translation rate, spontaneous loss of pluripotency, and compromised differentiation potential. METTL5-deficient mice are born at non-Mendelian rates and develop morphological and behavioral abnormalities. Importantly, mice lacking METTL5 recapitulate symptoms of patients with DNA variants in METTL5, thereby providing a new mouse disease model. Overall, our biochemical, molecular, and in vivo characterization highlights the importance of m(6)A in rRNA in stemness, differentiation, development, and diseases. |
