Nucleotide modifications and tRNA anticodon–mRNA codon interactions on the ribosome

Abstract

We have carried out molecular dynamics simulations of the tRNA anticodon and mRNA codon, inside the ribosome, to study the effect of the common tRNA modifications cmo 5 U34 and m 6 A37. In tRNA Val , these modifications allow all four nucleotides to be successfully read at the wobble position in a codon. Previous data suggest that entropic effects are mainly responsible for the extended reading capabilities, but detailed mechanisms have remained unknown. We have performed a wide range of simulations to elucidate the details of these mechanisms at the atomic level and quantify their effects: extensive free energy perturbation coupled with umbrella sampling, entropy calculations of tRNA (free and bound to the ribosome), and thorough structural analysis of the ribosomal decoding center. No prestructuring effect on the tRNA anticodon stem-loop from the two modifications could be observed, but we identified two mechanisms that may contribute to the expanded decoding capability by the modifications: The further reach of the cmo 5 U34 allows an alternative outer conformation to be formed for the noncognate base pairs, and the modification results in increased contacts between tRNA, mRNA, and the ribosome.

Retracted Article: Bioinformatic Analysis of Codon Usage and Phylogenetic Relationships in Different Genotypes of the Hepatitis C Virus

“…These findings showed that all of the transfer RNAs (tRNA) had C and G in the first nucleotides for anti-codon usage among all of the amino acids and, consequently, codon-anti-codon interaction in messenger RNA (mRNA) translation would be very strong. As a result, the average binding energy in codon-anti-codon interaction in hepatitis C is more than that with human cell interaction with HCV, and the mRNA and tRNA translation is stronger here than among similar human cell components (30). Based on the nucleotide structure of the codons, different used codons have special interactive affinity to anti-codons, and this thus leads to different powers of translation.…”

A deafness-associated tRNAAspmutation alters the m1G37 modification, aminoacylation and stability of tRNAAspand mitochondrial function

“…As shown in Figure 1, the m.7551A > G mutation is localized at a highly conserved nucleotide (A37), adjacent (3′) to the anticodon of mt–tRNA Asp (22,23). There were no modifications of i 6 A37 or t 6 A37 in the human mitochondrial tRNA Asp (27), although the nucleotides at position 37 (A or G) of tRNAs are often modified by methylthiolation (28–29). The modifications at position 37 were shown to contribute to the high fidelity of codon recognition and to the structural formation and stabilization of functional tRNAs (30–33).…”

Structural effects of modified ribonucleotides and magnesium in transfer RNAs

“…[28,29,30,31] In the present manuscript we report MD simulations of select tRNAs using the CHARMM36 force field[32] that was recently extended to included modified nucleotides. The simulations are designed to investigate the influence of the nucleotide modifications on tRNA structure and dynamics as well as the impact of Mg 2+ .…”