Abstract:

<p>Modifications in the tRNA anticodon loop, adjacent to the three-nucleotide anticodon, influence translation fidelity by stabilizing the tRNA to allow for accurate reading of the mRNA genetic code. One example is the N1-methylguaonosine modification at guanine nucleotide 37 (mG37) located in the anticodon loop, immediately adjacent to the anticodon nucleotides 34-36. The absence of mG37 in tRNA causes +1 frameshifting on polynucleotide, slippery codons. Here, we report structures of the bacterial ribosome containing tRNA bound to either cognate or slippery codons to determine how the mG37 modification prevents mRNA frameshifting. The structures reveal that certain codon-anticodon contexts and mG37 destabilize interactions of tRNA with the peptidyl site, causing large conformational changes typically only seen during EF-G mediated translocation of the mRNA-tRNA pairs. These studies provide molecular insights into how mG37 stabilizes the interactions of tRNA with the ribosome and the influence of slippery codons on the mRNA reading frame.</p>