Idiosyncratic tuning of tRNAs to achieve uniform ribosome binding

Abstract

The binding of seven tRNA anticodons to their complementary codons on Escherichia coli ribosomes was substantially impaired, as compared with the binding of their natural tRNAs, when they were transplanted into tRNA(2)(Ala). An analysis of chimeras composed of tRNA(2)(Ala) and various amounts of either tRNA(3)(Gly) or tRNA(2)(Arg) indicates that the presence of the parental 32-38 nucleotide pair is sufficient to restore ribosome binding of the transplanted anticodons. Furthermore, mutagenesis of tRNA(2)(Ala) showed that its highly conserved A32-U38 pair serves to weaken ribosome affinity. We propose that this negative binding determinant is used to offset the very tight codon-anticodon interaction of tRNA(2)(Ala). This suggests that each tRNA sequence has coevolved with its anticodon to tune ribosome affinity to a value that is the same for all tRNAs.

Analysis of genomic tRNA sets from Bacteria, Archaea, and Eukarya points to anticodon–codon hydrogen bonds as a major determinant of tRNA compositional variations

“…The experimental evidence points to the fact that in this group the weaker anticodons tend to correspond to the distant pair composition that improves ribosomal binding, while the stronger anticodons display correlation with the occurrence of the bindingimpeding motifs (Yarus et al 1986;Yarus and Smith 1995;Ashraf et al 2000). These findings are in a good agreement with the results obtained by Uhlenbeck's group on optimization of aa-tRNA structure (Olejniczak et al 2005).…”

“…Nucleotides 32-38 are demonstrated to form a tertiary non-Watson-Crick (Quigley and Rich 1976;Auffinger and Westhof 2001) or Watson-Crick (Olejniczak et al 2005) pair. This is the locus where the covariations with anticodon nucleotides are present in the tRNAs of all three domains of life.…”

“…Therefore, Y27-R43 pairs may affect energy generated by tRNA in its distorted conformation that may be required for tRNA translocation and release. Another possible explanation of this covariation is the tendency of the tRNA body to compensate the anticodon input to binding that would ultimately result in uniformity of translation of various aa-tRNAs (Dale and Uhlenbeck 2005a,b;Olejniczak et al 2005). Since there are no data on contribution of Y-R versus R-Y pairs to structural, thermodynamic, or kinetic parameters of tRNA, there is still a possibility that the Y27-R43 pair is a negative determinant that weakens binding of tRNAs forming three hydrogen bonds by nt 36, thus contributing to uniformity of translation of various aa-tRNAs.…”

Celebrating wobble decoding: Half a century and still much is new

“…The A 32 •U 38 interaction, highly conserved in tRNA Ala and also seen in tRNA Pro , decreases the tRNA affinity to the ribosomal A-site compared with other N 32 ○N 38 intraloop hydrogen bonding nucleosides. 66 Five Mycoplasma capricolum tRNA species with the unmodified anticodon UNN and decoding for five different amino acids have anticodon loop sequences with C 32 ○A 38 . In addition, tRNA Ala UGC has an intraloop interaction of C 32 ○C 38 .…”

An alternative to the RNA World Hypothesis

“…[75][76][77] The strengths of codon-anticodon interactions vary, with important contributions coming from G-C triple hydrogen bonds and stabilization of G-C base pairs by A-minor interactions. Among the most stable codon-anticodon interactions are those involving GGC, GCC, and GAC anticodons, 78 and the GAC anticodon binds more tightly to the GUC codon than the GAA anticodon to the UUC codon. 79 Therefore, interactions of GNC codons with their corresponding anticodons in the earliest ribosomal process would have been among the most stable.…”