Optimal Translational Termination Requires C4 Lysyl Hydroxylation of eRF1

被引:92
作者
Feng, Tianshu [1 ]
Yamamoto, Atsushi [1 ]
Wilkins, Sarah E. [2 ]
Sokolova, Elizaveta [3 ]
Yates, Luke A. [4 ]
Muenzel, Martin [2 ]
Singh, Pooja [1 ]
Hopkinson, Richard J. [2 ]
Fischer, Roman [5 ]
Cockman, Matthew E. [1 ]
Shelley, Jake [1 ]
Trudgian, David C. [6 ]
Schoedel, Johannes [7 ]
McCullagh, James S. O. [2 ]
Ge, Wei [2 ]
Kessler, Benedikt M. [5 ]
Gilbert, Robert J. [4 ]
Frolova, Ludmila Y. [3 ]
Alkalaeva, Elena [3 ]
Ratcliffe, Peter J. [1 ]
Schofield, Christopher J. [2 ]
Coleman, Mathew L. [1 ]
机构
[1] Univ Oxford, Ctr Cellular & Mol Physiol, Oxford OX3 7BN, England
[2] Univ Oxford, Chem Res Lab, Oxford OX1 3TA, England
[3] Russian Acad Sci, Engelhardt Inst Mol Biol, Moscow 119991, Russia
[4] Univ Oxford, Divis Struct Biol, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England
[5] Univ Oxford, Nuffield Dept Med, Target Discovery Inst, Oxford OX3 7FZ, England
[6] Univ Texas SW Med Ctr Dallas, Biochem Dept & Prote Core, Dallas, TX 75390 USA
[7] Univ Erlangen Nurnberg, Dept Hypertens & Nephrol, D-91054 Erlangen, Germany
基金
英国生物技术与生命科学研究理事会; 英国惠康基金; 俄罗斯基础研究基金会;
关键词
STOP CODON RECOGNITION; RELEASE FACTOR ERF1; TRANSFER-RNA; CRYSTAL-STRUCTURE; REPORTER SYSTEM; MESSENGER-RNA; DOMAIN; PROTEIN; JMJD6; 2-OXOGLUTARATE;
D O I
10.1016/j.molcel.2013.12.028
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:645 / 654
页数:10
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