6GFN

METTL16 MTase domain

Summary for 6GFN

• Entry DOI: 10.2210/pdb6gfn/pdb
• Related: 6GFK
• Descriptor: U6 small nuclear RNA (adenine-(43)-N(6))-methyltransferase, S-ADENOSYL-L-HOMOCYSTEINE (3 entities in total)
• Functional Keywords: rna sam methyltransferase, transferase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 33729.95

Authors

Chen, K.M.,Mendel, M.,Homolka, D.,McCarthy, A.A.,Pillai, R.S. (deposition date: 2018-05-01, release date: 2018-09-19, Last modification date: 2024-01-17)

Primary citation

Mendel, M.,Chen, K.M.,Homolka, D.,Gos, P.,Pandey, R.R.,McCarthy, A.A.,Pillai, R.S.
Methylation of Structured RNA by the m6A Writer METTL16 Is Essential for Mouse Embryonic Development.
Mol. Cell, 71:986-1000.e11, 2018

PubMed Abstract: Internal modification of RNAs with N-methyladenosine (mA) 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 mA 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 mA RNA methyltransferase in facilitating early development via regulation of SAM availability.

PubMed: 30197299
DOI: 10.1016/j.molcel.2018.08.004

Experimental method

X-RAY DIFFRACTION (2.86 Å)