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Series GSE116329 Query DataSets for GSE116329
Status Public on Sep 12, 2018
Title Methylation of structured RNA by the m6A writer METTL16 is essential for mouse embryonic development
Organisms Mus musculus; synthetic RNA
Experiment type Expression profiling by high throughput sequencing
Summary Internal modification of RNAs with N6-methyladenosine (m6A) is a highly conserved and widely used means of gene expression control. METTL16 is an m6A writer but how it recognizes its RNA targets and its physiological roles remain unknown. Here we describe the crystal structure of human METTL16 to reveal a classical methyltransferase domain but with an extra N-terminal module that is essential for catalysis. Together, they form a deep-cut groove lined by highly conserved positively charged residues that are essential for RNA binding and methylation activity. When given a random pool of RNAs, METTL16 selects structured RNAs for m6A methylation. We demonstrate that mouse Mettl16 is essential for early embryonic development, and acts via regulation of the SAM synthetase Mat2a mRNA. Our results highlight the pivotal role of an m6A RNA methyltransferase in facilitating early developmental decisions via regulation of SAM availability.
Overall design RNA sequencing was used to identify transcript abundance differences between Mettl16 mutant and control in E2.5 and E3.5 mouse embryos. In vitro RNA methylation assay with METTL16 followed by m6A immunoprecipitation and sequencing was used to identify METTL16 preferred targets.
Contributor(s) Mendel M, Chen K, Homolka D, Gos P, Pandey RR, McCarthy AA, Pillai RS
Citation(s) 30197299, 33930289
Submission date Jun 27, 2018
Last update date Jul 02, 2021
Contact name Ramesh Pillai
Organization name University of Geneva
Department Department of Molecular Biology
Street address 30, Quai Ernest-Ansermet
City Gneveva
ZIP/Postal code CH-1211
Country Switzerland
Platforms (2)
GPL19057 Illumina NextSeq 500 (Mus musculus)
GPL24911 Illumina HiSeq 2000 (synthetic RNA)
Samples (74)
GSM3228137 MM14_E2.5_Mettl16_HET
GSM3228138 MM15_E2.5_Mettl16_HET
GSM3228139 MM16_E2.5_Mettl16_KO
BioProject PRJNA478194
SRA SRP151443

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Supplementary file Size Download File type/resource
GSE116329_Mettl16_featureCounts_table_E2.5.csv.gz 14.6 Mb (ftp)(http) CSV
GSE116329_Mettl16_featureCounts_table_E3.5.csv.gz 17.8 Mb (ftp)(http) CSV
GSE116329_Mettl16_in_vitro_meth_table.csv.gz 2.8 Mb (ftp)(http) CSV
GSE116329_Mettl16_salmon_table_E2.5.csv.gz 1.4 Mb (ftp)(http) CSV
GSE116329_Mettl16_salmon_table_E3.5.csv.gz 1.7 Mb (ftp)(http) CSV
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