Wobble uridine tRNA modification: a new vulnerability of refractory melanoma

The enzymes catalysing the modification of the wobble uridine (U₃₄) of tRNAs (U₃₄-enzymes) play an important role in tumor development. We have recently demonstrated that the U₃₄-enzymes are crucial in the survival of glycolytic melanoma cultures through a codon-specific regulation of HIF1α mRNA translation. Moreover, depletion of U₃₄-enzymes resensitizes resistant melanoma to targeted therapy. These results indicate that targeting U₃₄-enzymes represents a new therapeutic opportunity for melanoma patients.