Optimal translational termination requires C4 lysyl hydroxylation of eRF1.
Feng T., Yamamoto A., Wilkins SE., Sokolova E., Yates LA., Münzel M., Singh P., Hopkinson RJ., Fischer R., Cockman ME., Shelley J., Trudgian DC., Schödel J., McCullagh JSO., Ge W., Kessler BM., Gilbert RJ., Frolova LY., Alkalaeva E., Ratcliffe PJ., Schofield CJ., Coleman ML.
Efficient stop codon recognition and peptidyl-tRNA hydrolysis are essential in order to terminate translational elongation and maintain protein sequence fidelity. Eukaryotic translational termination is mediated by a release factor complex that includes eukaryotic release factor 1 (eRF1) and eRF3. The N terminus of eRF1 contains highly conserved sequence motifs that couple stop codon recognition at the ribosomal A site to peptidyl-tRNA hydrolysis. We reveal that Jumonji domain-containing 4 (Jmjd4), a 2-oxoglutarate- and Fe(II)-dependent oxygenase, catalyzes carbon 4 (C4) lysyl hydroxylation of eRF1. This posttranslational modification takes place at an invariant lysine within the eRF1 NIKS motif and is required for optimal translational termination efficiency. These findings further highlight the role of 2-oxoglutarate/Fe(II) oxygenases in fundamental cellular processes and provide additional evidence that ensuring fidelity of protein translation is a major role of hydroxylation.