| First Author | Mendel M | Year | 2018 |
| Journal | Mol Cell | Volume | 71 |
| Issue | 6 | Pages | 986-1000.e11 |
| PubMed ID | 30197299 | Mgi Jnum | J:265047 |
| Mgi Id | MGI:6199095 | Doi | 10.1016/j.molcel.2018.08.004 |
| Citation | Mendel M, et al. (2018) Methylation of Structured RNA by the m(6)A Writer METTL16 Is Essential for Mouse Embryonic Development. Mol Cell |
| abstractText | Internal modification of RNAs with N(6)-methyladenosine (m(6)A) is a highly conserved means of gene expression control. While the METTL3/METTL14 heterodimer adds this mark on thousands of transcripts in a single-stranded context, the substrate requirements and physiological roles of the second m(6)A writer METTL16 remain unknown. Here we describe the crystal structure of human METTL16 to reveal a methyltransferase domain furnished with an extra N-terminal module, which together form a deep-cut groove that is essential for RNA binding. When presented with a random pool of RNAs, METTL16 selects for methylation-structured RNAs where the critical adenosine is present in a bulge. Mouse 16-cell embryos lacking Mettl16 display reduced mRNA levels of its methylation target, the SAM synthetase Mat2a. The consequence is massive transcriptome dysregulation in approximately 64-cell blastocysts that are unfit for further development. This highlights the role of an m(6)A RNA methyltransferase in facilitating early development via regulation of SAM availability. |
