Mitochondrial RNA modifications shape metabolic plasticity in metastasis

Abstract Aggressive and metastatic cancers show enhanced metabolic plasticity 1 , but the precise underlying mechanisms of this remain unclear. Here we show how two NOP2/Sun RNA methyltransferase 3 (NSUN3)-dependent RNA modifications—5-methylcytosine (m 5 C) and its derivative 5-formylcytosine (f 5 C) (refs. 2–4 )—drive the translation of mitochondrial mRNA to power metastasis. Translation of mitochondrially encoded subunits of the oxidative phosphorylation complex depends on the formation of m 5 C at position 34 in mitochondrial tRNA Met . m 5 C-deficient human oral cancer cells exhibit increased levels of glycolysis and changes in their mitochondrial function that do not affect cell viability or primary…

• BS
  Bristol-Myers Squibb
• DK
  Deutsches Krebsforschungszentrum
• CR
  Cancer Research UK
• CS
  China Scholarship Council

  Award: 201708330262
• FL
  Fonds Léon Fredericq