title: An active role for tRNA in decoding beyond codon:anticodon pairing.
abstract: During transfer RNA (tRNA) selection, a cognate codon:anticodon interaction triggers a series of events that ultimately results in the acceptance of that tRNA into the ribosome for peptide-bond formation. High-fidelity discrimination between the cognate tRNA and near- and noncognate ones depends both on their differential dissociation rates from the ribosome and on specific acceleration of forward rate constants by cognate species. Here we show that a mutant tRNA(Trp) carrying a single substitution in its D-arm achieves elevated levels of miscoding by accelerating these forward rate constants independent of codon:anticodon pairing in the decoding center. These data provide evidence for a direct role for tRNA in signaling its own acceptance during decoding and support its fundamental role during the evolution of protein synthesis.
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Luisa
authors.initials: L
authors.lastname: Cochella
authors.forename: Rachel
authors.initials: R
authors.lastname: Green
mesh_terms: D000926:Anticodon; D020029:Base Pairing; D003062:Codon; D018388:Codon, Terminator; D004151:Dipeptides / Q000096:biosynthesis; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006868:Hydrolysis; D007700:Kinetics; D009154:Mutation; D009690:Nucleic Acid Conformation; D010444:Peptide Elongation Factor Tu / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D012364:RNA, Transfer, Trp / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism*
chemical_list: D000926:Anticodon; D003062:Codon; D018388:Codon, Terminator; D004151:Dipeptides; D012333:RNA, Messenger; D012364:RNA, Transfer, Trp; D006160:Guanosine Triphosphate; D020558:GTP Phosphohydrolases; D010444:Peptide Elongation Factor Tu