An Active Role for tRNA in Decoding Beyond Codon:Anticodon Pairing

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Science  20 May 2005:
Vol. 308, Issue 5725, pp. 1178-1180
DOI: 10.1126/science.1111408

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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 tRNATrp 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.

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