Transcriptome-wide reprogramming of N6-methyladenosine modification by the mouse microbiome

Microbiome affects many aspects of human health and disease and elicits a wide range of host responses including remarkable epigenetic changes such as DNA methylation, histone modification and non-coding RNA expression. 1 A still poorly explored area of microbiome-host interaction is the response of host RNA modification. N 6 -methyladenosine (m 6 A) is the most abundant mRNA modification in mammalian cells, occurring at ~3 modified adenosine residues per transcript. The m 6 A mapping and biology have been extensively studied recently. 2 At the physiological level, m 6 A affects embryonic development, circadian clock, immuno-response, and others. At the cellular and molecular level, m 6 A affects all key aspects of mRNA processing, translation and decay. Importantly, m 6 A is a predominant, transcriptome-wide mark that is responsive to environmental changes; this dynamic m 6 A pattern is maintained by the writer enzyme complex containing the METTL3 and METTL14 proteins, and two eraser enzymes of FTO and ALKBH5. 3 , 4