Emerging Understanding of Translation Termination

The existence of a protein with RF activity in eukaryThe termination of protein synthesis takes place on the otes was demonstrated some twenty years ago in rabbit ribosomes as a response to a stop, rather than a sense reticulocytes (Konecki et al., 1977). After two decades codon in the ’decoding’ site (A site). Translation terminaof investigation, a eukaryotic protein family with the tion requires two classes of polypeptide release factors properties of RFs, designated eRF-1, was discovered (RFs): one, codon-specific (RF-1 and RF-2 in prokary(Frolova et al., 1994). It includes a Sup45 protein of otes; eRF-1 in eukaryotes) and the other, non-specific Saccharomyces cerevisiae that is involved in suppres(RF-3 in prokaryotes; eRF-3 in eukaryotes). The underlysion of three nonsense codons (i.e., omnipotent suping mechanism for translation termination represents a pression) during translation (reviewed by Stansfield and long-standing coding problem of considerable interest. Tuite, 1994). A GTP requirement for polypeptide release It entails protein–RNA recognition instead of the wellwas also demonstrated in rabbit reticulocytes (Konecki understood codon–anticodon pairing during the mRNA– et al., 1977). Eukaryotic counterparts of bacterial RF-3 tRNA interaction (reviewed by Tate and Brown, 1992). were identified recently and are referred to as eRF-3 The fact that two RFs from bacteria (RF-1, UAG/UAA (Zhouravleva et al., 1995). The eRF-3 family includes a specific; RF-2, UGA/UAA specific) exhibit codon speciSup35 protein of S. cerevisiae that carries G-domain ficity suggests that they must interact directly with the motifs and is involved in omnipotent suppression of codon. This model is supported by protein–RNA crossnonsense codons (Stansfield and Tuite, 1994). Like baclinking data that provide evidence for close contact beterial RF-3, the loss of Sup35 increases misreading of tween the stop codon and RF (Tate and Brown, 1992, stop codons, and an excess of Sup35 in concert with and references therein). Important clues to the mechaSup45 stimulates polypeptide termination. Unlike RF-3 nism of stop codon recognition and polypeptide termiin bacteria, however, Sup35 is essential for cell growth nation are now emerging as a result of the identification of yeast. It is likely that most of the essential players of of the RF-encoding genes, functional studies of mupolypeptide termination have now appeared on stage. tants, and the high-level expression of the correspondRF-tRNA Molecular Mimicry ing gene products for biochemical analysis. Upon accumulation of RF sequences from different or-