PerspectiveMolecular Biology

Internal mRNA Methylation Finally Finds Functions

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Science  14 Mar 2014:
Vol. 343, Issue 6176, pp. 1207-1208
DOI: 10.1126/science.1249340

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Summary

Modification of internal adenosines in messenger RNA (mRNA) by methylation of the N6 position (m6A) was first observed almost four decades ago. Early work demonstrated that the m6A 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 (1) 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 m6A residues (2). The existence of a demethylase and the demonstration that m6A levels were raised when the enzyme was knocked down strongly suggested that at least some m6A modifications were reversible and might be subject to dynamic regulation. Since then, a series of papers have appeared in rapid succession, together providing a wealth of unequivocal evidence for m6A function. But these findings still have not led to a coherent picture of the number and variety of functions of the m6A modification.