Abstract
SummaryEfficient 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.
Highlights
Hydroxylation was historically considered a rare posttranslational modification largely restricted to proteins involved in extracellular matrix formation (Walsh, 2005)
We identify an uncharacterized JmjC 2OG oxygenase, Jmjd4, as a regulator of translational termination—a fundamental cellular process required for decoding stop codons and maintaining protein sequence fidelity
The most abundant activity-dependent Jmjd4 interactors were eukaryotic release factor 1 (eRF1) and eRF3a (Figure S1C), which are nonredundant proteins required for stop codon recognition and translational termination (Kisselev and Buckingham, 2000; Nakamura and Ito, 2011)
Summary
Hydroxylation was historically considered a rare posttranslational modification largely restricted to proteins involved in extracellular matrix formation (Walsh, 2005). Many protein hydroxylases belong to the family of 2-oxoglutarate (2OG)- and Fe(II)-dependent oxygenases (2OG oxygenases) that oxidizes diverse substrates, including lipid, nucleic acid, and small molecules (Kaelin and Ratcliffe, 2008; Klose et al, 2006; Loenarz and Schofield, 2011). A family of prolyl hydroxylases (PHD1–PHD3) that targets hypoxia-inducible transcription factor (HIF-a) for proteasomal degradation is inactivated by hypoxia (Kaelin and Ratcliffe, 2008; Loenarz and Schofield, 2008) In addition to their role in hypoxia signaling, 2OG oxygenases are involved in a variety of other fundamental cellular processes, such as chromatin remodeling. A subfamily of 2OG oxygenases with a common JmjC catalytic domain catalyzes histone demethylation via a hydroxylation reaction (Klose et al, 2006; Loenarz and Schofield, 2008)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
