Peptidyl-transfer RNA hydrolase prevents inhibition of protein synthesis initiation

Abstract

PEPTIDYL-tRNA HYDROLASE (called hydrolase below) catalyses the hydrolysis of peptides from peptidyl-tRNAs that are not bound to ribosomes^1,2 but will not hydrolyse amino acyl-tRNA or fMet-tRNA_f^Met. It is interesting that hydrolase seems to be ubiquitous in nature, it has been found in all cells where it has been sought, including yeast³, bacteria, rat liver and jackbeans⁴ However, the metabolic role of this enzyme has not been established It is required for normal function, as a mutant strain of Escherichia coli with a temperature-sensitive hydrolase cannot continue protein synthesis at the nonpermissive temperature⁵ Hydrolase itself is not required for initiation, elongation or termination phases of protein synthesis⁶ Menninger⁷ has shown that peptidyl-tRNA, formed on ribosomes, accumulates at nonpermissive temperatures in cells with the temperature-sensitive hydrolase. Hydrolase thus seems to be a scavenger enzyme of peptidyl-tRNAs normally aborted from ribosomes during protein synthesis Of interest now is why peptidyl-tRNA is frequently prematurely released from ribosomes and why protein synthesis is inhibited in the mutant strain with a defective hydrolase5 I report here work on the latter problem and present evidence which indicates that peptidyl-tRNAs accumulate and compete with N-formal-Met tRNA_f^Met during initiation of protein synthesis.