Reversible RNA adenosine methylation in biological regulation

N⁶-methyladenosine (m⁶A) is a ubiquitous modification in mRNA and other RNAs across most eukaryotes. For many years, however, the exact functions of m⁶A were not clearly understood. The discovery that the fat mass and obesity-associated protein (FTO) is an m⁶A demethylase indicates that this modification is reversible and dynamically regulated, suggesting that it has regulatory roles. In addition, it has been shown that m⁶A affects cell fate decisions in yeast and plant development. Recent affinity-based m⁶A profiling in mouse and human cells further showed that this modification is a widespread mark in coding and noncoding RNA (ncRNA) transcripts and is likely dynamically regulated throughout developmental processes. Therefore, reversible RNA methylation, analogous to reversible DNA and histone modifications, may affect gene expression and cell fate decisions by modulating multiple RNA-related cellular pathways, which potentially provides rapid responses to various cellular and environmental signals, including energy and nutrient availability in mammals.