Abstract

A molecular modification called m6Am has been found to regulate the stability of messenger RNAs in mammalian cells. The mechanism casts fresh light on how reversibly modified RNA bases control the fate of mRNA. See Article p.371 Recent studies have highlighted the role of reversible modifications, such as the addition of a methyl group to adenosines (m6A), on RNA function. Samie Jaffrey and colleagues show that a dimethyl-modified base (m6Am) at the 5′ end of certain mRNAs, next to the 7-methylguanosine cap structure, can positively influence mRNA stability by preventing their DCP2-mediated decapping. This modification is itself regulated by the fat mass and obesity-associated protein FTO, a demethylase that exhibits a preference for m6Am over m6A. This work provides insight into the biological importance of FTO, which has been implicated in body weight regulation.

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