Emerging Understanding of Translation Termination

Most textbooks end the description of protein synthesis with the RF-mediated release of the completed polypeptide chain from the peptidyl tRNA. This is a gross oversight because there is an additional crucial step in protein synthesis: recycling of ribosomes through decomposition of the termination complex (Hirashima and Kaji 1970xHirashima, A. and Kaji, A. Biochem. Biophys. Res. Communs. 1970; 41: 877–883Crossref | PubMed | Scopus (33)See all ReferencesHirashima and Kaji 1970). In bacteria, this process requires a ribosome recycling factor (RRF, originally called ribosome releasing factor; Janosi et al. 1994xJanosi, L., Shimizu, I., and Kaji, A. Proc. Natl. Acad. Sci. USA. 1994; 91: 4249–4253Crossref | PubMedSee all ReferencesJanosi et al. 1994). This process is fundamental because the gene for RRF is essential for cell growth and the living cell must reuse the ribosome, RF, and tRNA for the next round of protein synthesis.Where does RRF bind and how does it work? Upon release of the polypeptide chain, the ribosomal A site remains occupied with a tRNA-mimicking RF protein. A translocase is probably required to forward deacylated tRNA and RF to the E and P sites of the ribosome, respectively. We speculate that RF-3 or EF-G may catalyze this final translocation reaction. RRF is known to act in vitro on a complex of mRNA with ribosomes having an empty A site and bound deacylated tRNA at the P site (Hirashima and Kaji 1970xHirashima, A. and Kaji, A. Biochem. Biophys. Res. Communs. 1970; 41: 877–883Crossref | PubMed | Scopus (33)See all ReferencesHirashima and Kaji 1970). Therefore, it is tempting to speculate that RRF also has a tRNA-mimicry domain for binding to the A site of the ribosome. The mechanism of decomposition of the termination complex by RRF and the eukaryotic RRF proteins remains to be investigated.