Download MendeleyMethylation of Structured RNA by the m6A Writer METTL16 Is Essential for Mouse Embryonic Development.
Mendel, M., Chen, K.M., Homolka, D., Gos, P., Pandey, R.R., McCarthy, A.A., Pillai, R.S.(2018) Mol Cell 71: 986-1000.e11
- PubMed: 30197299
- DOI: https://doi.org/10.1016/j.molcel.2018.08.004
- Primary Citation of Related Structures:
6GFK, 6GFN, 6GT5 - PubMed Abstract:
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 ∼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.
Organizational Affiliation:
Department of Molecular Biology, Science III, University of Geneva, 30 Quai Ernest-Ansermet, CH-1211 Geneva 4, Switzerland.
