An unusual condition of leucine transfer RNA appearing during leucine starvation of Escherichia coli

Maintenance of accuracy during amino acid starvation

“…The concentration of acylated tRNA will thus never be completely reduced proportionally to the aminoacylation level. This is consistent with the finding that a large portion (8-40%) of the 'starved' tRNA remains in the acylated form during amino acid starvation [3][4][5]. The pools of cognate aminoacyl-tRNA bound to the ribosomal A-and P-sites may stay almost unchanged for rather large reductions in aminoacylation.…”

“…The EFTu.ppGpp complex may possibly also facilitate the binding of uncharged tRNA to the ribosome, perhaps by forming a ternary complex with the uncharged tRNA. (In fact, certain uncharged tRNAs have been observed to carry an unidentified molecular group which protects them from degradation during amino acid starvation [3].) This action of ppGpp would reduce the elongation rate generally and specifically at the starved codon, and together with the reduced levels of rRNA, tRNA, and mRNA, this could explain the observed inhibition of protein synthesis during severe amino acid starvation.…”

“…During mild starvation in both animal cells [5,15] and relA-cells [3], or when the action of ppGpp is excluded for relA ÷ cells [4], the rate of protein synthesis is surprisingly little affected. Even if there is a reduction of the elongation rate at hungry codons, it does not need to affect the overall rate of protein synthesis, as has been pointed out in previous work [15,16].…”

Elongation factor Tu.guanosine 3'-diphosphate 5'-diphosphate complex increases the fidelity of proofreading in protein biosynthesis: mechanism for reducing translational errors introduced by amino acid starvation.

“…The concentration of the limiting aminoacyl-tRNA would then increase, the balance of substrates would be restored, and translational accuracy would be retained. However, the levels of aminoacyl-tRNAs in amino acid starved rel' and rel-cells are not remarkably different (3)(4)(5), and the rate of polypeptide chain elongation in the presence of ppGpp is similar to that observed in its absence (11). These findings argue against a reduction in the consumption of the limiting aminoacyltRNA.…”

“…For example, when two substrates, one cognate and the other near-cognate, compete for the active site of an enzyme, the error rate (E) will be equal to the relative rates of the cognate (Vc) and the near-cognate (Vn) reactions, and this ratio should be determined by the product of the relative rate constants for the cognate (Ic) and near-cognate (kn) reactions and the relative concentrations of the cognate ([C]) and near-cognate ([N]) substrates (1,2). E= Vn kn [N] Vc kc [C] When Escherichia coli are starved for an amino acid, the concentration of that aminoacyl-tRNA is reduced by a factor of4 (3)(4)(5). This should lead to a proportionate reduction in the concentration of the corresponding ternary complex, elongation factor Tu (EF-Tu)-GTP-aminoacyl-tRNA, and hence in its ability to compete with near-cognate ternary complexes for reaction with the ribosome (2).…”