Novel base-pairing interactions at the tRNA wobble position crucial for accurate reading of the genetic code

Alexey Rozov (1) , Natalia Demeshkina (1) , Iskander Khusainov (1, 2) , Eric Westhof (3) , Marat M. Yusupov (1) , Gulnara Yusupova (1)

1 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire
2 Institute of Fundamental Medicine and Biology [Kazan, Russia]
3 ARN - Architecture et Réactivité de l'ARN

Posttranscriptional modifications at the wobble position of transfer RNAs play a substantial role in deciphering the degenerate genetic code on the ribosome. The number and variety of modifications suggest different mechanisms of action during messenger RNA decoding, of which only a few were described so far. Here, on the basis of several 70S ribosome complex X-ray structures, we demonstrate how Escherichia coli tRNA(Lys)(UUU) with hypermodified 5-methylaminomethyl-2-thiouridine (mnm(5)s(2)U) at the wobble position discriminates between cognate codons AAA and AAG, and near-cognate stop codon UAA or isoleucine codon AUA, with which it forms pyrimidine-pyrimidine mismatches. We show that mnm(5)s(2)U forms an unusual pair with guanosine at the wobble position that expands general knowledge on the degeneracy of the genetic code and specifies a powerful role of tRNA modifications in translation. Our models consolidate the translational fidelity mechanism proposed previously where the steric complementarity and shape acceptance dominate the decoding mechanism.

Domaines: Biochimie, Biologie Moléculaire; Sciences du Vivant [q-bio]; Biologie moléculaire

Alexey Rozov, Natalia Demeshkina, Iskander Khusainov, Eric Westhof, Marat M. Yusupov, et al.. Novel base-pairing interactions at the tRNA wobble position crucial for accurate reading of the genetic code. Nature Communications, 2016, 7 (1), pp.10457. ⟨10.1038/ncomms10457⟩. ⟨hal-02294521⟩