N6-Methyladenosine in Nuclear RNA is a Major Substrate of the Obesity-Associated FTO

摘要

We report here that FTO (fat mass and obesity-associated protein) exhibits efficient oxidative demethylation activity of abundant N⁶-methyladenosine (m⁶A) residues in RNA in vitro. FTO knockdown with siRNA led to an increased level of m⁶A in mRNA, whereas overexpression of FTO resulted in a decreased level of m⁶A in human cells. We further show that FTO partially colocalizes with nuclear speckles, supporting m⁶A in nuclear RNA as a physiological substrate of FTO.