This base modification is present on average in ~3 sites of every mRNA in mammals. The internal N6-methyladenosine (m6A) modification in messenger RNA is one of the most abundant RNA modifications in eukaryotes. Understanding the scope and mechanisms of dynamic RNA modifications thus represents an emerging research frontier in biology and medicine. Some RNA modifications are dynamic and may have critical regulatory roles analogous to those of protein and DNA modifications. We revealed functional roles of DNA 6-methyladenosine (6mA) in eukaryotic genomes and studied metal ion homeostasis and selective metal ion recognition by naturally occurring and engineered proteins.Ĭellular RNAs contain more than a hundred fifty structurally distinct post-transcriptional modifications at thousands of sites. We developed enabling methods to map DNA 5-hydroxymethylcytosine (5hmC) and its oxidation derivatives in mammalian genomes and invented new genomic methods to accurately monitor transcription and chromatin state. We discovered the first RNA demethylase and uncovered transcriptional and post-transcriptional gene expression regulation pathways mediated by dynamic RNA modifications such as N6-methyladenosine (m6A). Our research program spans a broad range of chemical biology, nucleic acid chemistry and biology, epigenetics, and bioinorganic chemistry. We study dynamic and reversible RNA and DNA methylation in gene expression regulation with chemical and biological tools.