PLX228573

GSE78040 (mouse): Reversible methylation of m6Am in the 5 cap controls mRNA stability

• Organsim mouse
• Type RNASEQ
• Target gene
• Project ARCHS4

Internal bases in mRNA can be subjected to modifications that influence the fate of mRNA in cells. One of the most prevalent modified bases is found at the 5 end of mRNA, at the first encoded nucleotide adjacent to the 7-methylguanosine cap. Here we show that this nucleotide, N6,2-O-dimethyladenosine (m6Am), is a reversible modification that influences cellular mRNA fate. Using a transcriptome-wide map of m6Am we find that m6Am-initiated transcripts are markedly more stable than mRNAs that begin with other nucleotides. We show that the enhanced stability of m6Am-initiated transcripts is due to resistance to the mRNA-decapping enzyme DCP2. Moreover, we find that m6Am is selectively demethylated by fat mass and obesity-associated protein (FTO). FTO preferentially demethylates m6Am rather than N6-methyladenosine (m6A), and reduces the stability of m6Am mRNAs. Together, these findings show that the methylation status of m6Am in the 5 cap is a dynamic and reversible epitranscriptomic modification that determines mRNA stability. SOURCE: Jan Mauer (jan.mauer@gmail.com) - Weill Medical College, Cornell University