First Author | Xing M | Year | 2020 |
Journal | EMBO Rep | Volume | 21 |
Issue | 10 | Pages | e49863 |
PubMed ID | 32783360 | Mgi Jnum | J:301381 |
Mgi Id | MGI:6505165 | Doi | 10.15252/embr.201949863 |
Citation | Xing M, et al. (2020) The 18S rRNA m(6) A methyltransferase METTL5 promotes mouse embryonic stem cell differentiation. EMBO Rep 21(10):e49863 |
abstractText | RNA modifications represent a novel layer of regulation of gene expression. Functional experiments revealed that N(6) -methyladenosine (m(6) A) on messenger RNA (mRNA) plays critical roles in cell fate determination and development. m(6) A mark also resides in the decoding center of 18S ribosomal RNA (rRNA); however, the biological function of m(6) A on 18S rRNA is still poorly understood. Here, we report that methyltransferase-like 5 (METTL5) methylates 18S rRNA both in vivo and in vitro, which is consistent with previous reports. Deletion of Mettl5 causes a dramatic differentiation defect in mouse embryonic stem cells (mESCs). Mechanistically, the m(6) A deposited by METTL5 is involved in regulating the efficient translation of F-box and WD repeat domain-containing 7 (FBXW7), a key regulator of cell differentiation. Deficiency of METTL5 reduces FBXW7 levels and leads to the accumulation of its substrate c-MYC, thereby delaying the onset of mESC differentiation. Our study uncovers an important role of METTL5-mediated 18S m(6) A in mESC differentiation through translation regulation and provides new insight into the functional significance of rRNA m(6) A. |