Mitochondrial RNA modifications shape metabolic plasticity in metastasis.

ABSTRACT: Aggressive and metastatic cancers show enhanced metabolic plasticity¹, 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 (m⁵C) and its derivative 5-formylcytosine (f⁵C) (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 m⁵C at position 34 in mitochondrial tRNA^Met. m⁵C-deficient human oral cancer cells exhibit increased levels of glycolysis and changes in their mitochondrial function that do not affect cell viability or primary tumour growth in vivo; however,

SUBMITTER: Delaunay S 

PROVIDER: S-EPMC9300468 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature