N6-Methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO

G Jia, YE Fu, XU Zhao, Q Dai, G Zheng, Y Yang… - Nature chemical …, 2011 - nature.com
G Jia, YE Fu, XU Zhao, Q Dai, G Zheng, Y Yang, C Yi, T Lindahl, T Pan, YG Yang, C He
Nature chemical biology, 2011nature.com
We report here that fat mass and obesity-associated protein (FTO) has efficient oxidative
demethylation activity targeting the abundant N 6-methyladenosine (m6A) residues in RNA
in vitro. FTO knockdown with siRNA led to increased amounts of m6A in mRNA, whereas
overexpression of FTO resulted in decreased amounts of m6A in human cells. We further
show the partial colocalization of FTO with nuclear speckles, which supports the notion that
m6A in nuclear RNA is a major physiological substrate of FTO.
Abstract
We report here that fat mass and obesity-associated protein (FTO) has efficient oxidative demethylation activity targeting the abundant N6-methyladenosine (m6A) residues in RNA in vitro. FTO knockdown with siRNA led to increased amounts of m6A in mRNA, whereas overexpression of FTO resulted in decreased amounts of m6A in human cells. We further show the partial colocalization of FTO with nuclear speckles, which supports the notion that m6A in nuclear RNA is a major physiological substrate of FTO.
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