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Methylation of Structured RNA by the m6A Writer METTL16 Is Essential for Mouse Embryonic Development.

  • Mendel M Department of Molecular Biology, Science III, University of Geneva, 30 Quai Ernest-Ansermet, CH-1211 Geneva 4, Switzerland.
  • Chen KM Department of Molecular Biology, Science III, University of Geneva, 30 Quai Ernest-Ansermet, CH-1211 Geneva 4, Switzerland.
  • Homolka D Department of Molecular Biology, Science III, University of Geneva, 30 Quai Ernest-Ansermet, CH-1211 Geneva 4, Switzerland.
  • Gos P Department of Molecular Biology, Science III, University of Geneva, 30 Quai Ernest-Ansermet, CH-1211 Geneva 4, Switzerland.
  • Pandey RR Department of Molecular Biology, Science III, University of Geneva, 30 Quai Ernest-Ansermet, CH-1211 Geneva 4, Switzerland.
  • McCarthy AA European Molecular Biology Laboratory, Grenoble Outstation, 71 Avenue des Martyrs, 38042 Grenoble, France.
  • Pillai RS Department of Molecular Biology, Science III, University of Geneva, 30 Quai Ernest-Ansermet, CH-1211 Geneva 4, Switzerland. Electronic address: ramesh.pillai@unige.ch.
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  • 2018-09-11
Published in:
  • Molecular cell. - 2018
METTL16
Mat2a
SAM availability
SAM synthetase
U6 snRNA
blastocysts
crystal structure
m(6)A
morula
splicing
Adenosine
Animals
Demethylation
Embryonic Development
Gene Expression
HEK293 Cells
Humans
Methionine Adenosyltransferase
Methylation
Methyltransferases
Mice
Mice, Knockout
RNA
RNA Processing, Post-Transcriptional
RNA, Messenger
RNA, Small Nuclear
English Internal modification of RNAs with N6-methyladenosine (m6A) 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 m6A 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 m6A RNA methyltransferase in facilitating early development via regulation of SAM availability.
Language
  • English
Open access status
hybrid
Identifiers
Persistent URL
https://folia.unifr.ch/global/documents/46803
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