7 Translation Termination, the Prion [PSI+], and Ribosomal Recycling

Abstract

Following completion of the elongation phase of protein synthesis (Chapters 2 and 3), the ribosome is brought into its pretermination complex when a stop (nonsense) codon is translocated into its A site (Fig. 1A). Stop codons are normally not read by tRNAs, but by class 1 release factor (RF) proteins (Scolnick et al. 1968; Caskey et al. 1970; Capecchi and Klein 1970). There are two RFs (RF1 and RF2) in eubacteria, one (eRF1) in eukaryotes and one (aRF1) in archaea. RF1 recognizes the stop codons UAG and UAA, RF2 recognizes UAA and UGA (Scolnick et al. 1968), and eRF1 and aRF1 recognize all three stop codons (Konecki et al. 1977). Although there are sequence homologies between RF1 and RF2, as well as between eRF1 and aRF1, there is only a single universal homology among all class 1 RFs: the GGQ (Gly Gly Gln) motif (Frolova et al. 1999). Binding of a class 1 RF to a ribosome programmed with its cognate stop codon (Fig. 1B) induces hydrolysis of the ester bond that links the completed protein with the tRNA bound to the P site (Fig. 1C), leading to rapid dissociation of the protein from the ribosome. This general scheme for the first phase of termination of protein synthesis (Caskey et al. 1977) is still valid, but the molecular details of stop codon recognition and induction of ester bond hydrolysis remain to be clarified.

In eubacteria and eukaryotes, but not in archaea, there exists a class 2 RF: the GTPases RF3...