Peptidyl-tRNA hydrolase and its critical role in protein biosynthesis

Abstract

Peptidyl-tRNA hydrolase (Pth) releases tRNA from peptidyl-tRNA by cleaving the ester bond between the peptide and the tRNA. Genetic analyses using Escherichia coli harbouring temperature-sensitive Pth have identified a number of translation factors involved in peptidyl-tRNA release. Accumulation of peptidyl-tRNA in the cells leads to depletion of aminoacyl-tRNA pools and halts protein biosynthesis. Thus, it is vital for cells to maintain Pth activity to deal with the pollution of peptidyl-tRNAs generated during the initiation, elongation and termination steps of protein biosynthesis. Interestingly, while eubacteria possess a single class of peptidyl-tRNA hydrolase, eukaryotes possess several such activities, making Pth a potential drug target to control eubacterial infections. This review discusses the aspects of Pth that relate to its history and biochemistry and its physiological connections with various cellular factors.

Unprecedented loss of ammonia assimilation capability in a urease-encoding bacterial mutualist

“…The two other frameshifted information transfer genes in B. vafer encode DNA primase ( dnaG ) and peptidyl-tRNA hydrolase ( pth ) (Figure 4). DnaG synthesizes short RNA primers essential for lagging strand DNA replication, whereas Pth plays an important role in maintaining efficient protein synthesis by cleaving peptidyl-tRNAs released from stalled ribosomes [26]. …”

RNA-binding Site of Escherichia coli Peptidyl-tRNA Hydrolase

“…Pth1 has been found to be essential in bacteria (1)(2)(3)8) but not in Saccharomyces cerevisiae (2,6,7). Therefore, the bacterial enzyme offers itself as an interesting potential target for new antibacterial drugs (9). In this context, the characterization of the interface between Pth1 and its substrate is important to guide the search for enzyme inhibitors.…”

Translation of a histone H3 tail as a model system for studying peptidyl-tRNA drop-off

“…This process possibly accompanies the dissociation of the ribosome complex [3], so that the ribosome can be re-used. Dropped-off peptidyl-tRNA is hydrolyzed at the ester bond between the peptide and tRNA by peptidyl-tRNA hydrolase (PTH), releasing tRNA from the sequestration [4]. The fact that PTH is essential for cell viabilities suggests that the frequency of peptidyl-tRNA drop-off cannot be ignored [4].…”

“…Dropped-off peptidyl-tRNA is hydrolyzed at the ester bond between the peptide and tRNA by peptidyl-tRNA hydrolase (PTH), releasing tRNA from the sequestration [4]. The fact that PTH is essential for cell viabilities suggests that the frequency of peptidyl-tRNA drop-off cannot be ignored [4]. Indeed, several kinds of tRNAs are sequestered as peptidyl-tRNAs in Escherichia coli with a temperature-sensitive PTH at an elevated temperature [5].…”