In a recent study, it was shown that mouse embryonic fibroblasts (MEFs) derived from Fto−/− mice exhibit slower rates of growth and have reduced mRNA translation when compared to WT MEFs.166 This seems to occur, at least in part, by maintenance of levels of Aminoacyl-tRNA synthetases (AARSs), as part of a large multimer complex known as the Multi-Synthetase Complex (MSC),167 which tether free amino-acids to their cognate tRNAs and are one of the key modulators of translation. Consistent with the reduced rates of translation, Fto−/− MEFs have reduced protein levels of MSC components. The defects in mRNA translation and reduced levels of MSC components in Fto−/− MEFs are rescued by re-expressing FTO in these cells, implicating a role for FTO in regulating translation rates through maintenance of MSC protein levels within the cell.166
