A Mechanistic Study Elucidates the Catalytic Activity of the Human FTO Enzyme
A recent study co-first-authored by Dr P. Maheswaran of the Department of Pharmacy has been published in the prestigious journal Nucleic Acids Research, offering significant new mechanistic insights into the function of the human fat mass and obesity-associated (FTO) enzyme, a key regulator of RNA modification. The research examines how FTO acts on N⁶-methyladenosine (m⁶A), one of the most abundant and biologically significant RNA modifications. While FTO has long been described as an RNA demethylase, the study demonstrates that its catalytic activity fundamentally differs from the prevailing view. Through the combined use of mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy, the authors show that FTO primarily catalyses the hydroxylation of m⁶A to form an N⁶-hydroxymethyladenosine (hm⁶A) intermediate, rather than directly generating demethylated adenosine. This mechanism contrasts sharply with that..
