Internal mRNA Methylation Finally Finds Functions

摘要

Modification of internal adenosines in messenger RNA (mRNA) by methylation of the N~6 position (m~6A) was first observed almost four decades ago. Early work demonstrated that the m~6A modification was quite common, occurring at an estimated frequency of three to five residues per mRNA. Nevertheless, the function, if any, of this modification remained enigmatic. The cloning in 1997 of a subunit of the RNA methylase complex was followed by a period of fitful inactivity before the field reawakened in 2011 with the discovery of an enzyme, FTO (fat mass and obesity-associated protein), that was shown to catalyze the demethylation of internal m~6A residues . The existence of a demethylase and the demonstration that m~6A levels were raised when the enzyme was knocked down strongly suggested that at least some m~6A modifications were reversible and might be subject to dynamic regulation.