The mechanism of translation termination has long been a puzzle. The release factor (RF) class of translation factors plays a key role in terminating protein synthesis. Bacteria have two RFs, RF1 and RF2, with high specificity to decipher three stop codons. Decades ago, an idea was formulated that RFs may be protein analogs of tRNA. This idea gained substantial support 10 years ago by the identification of two classes of crucial RF peptide motifs, P(A/V)T/SPF and GGQ, in bacteria. These motifs were functionally equivalent to the anticodon and aminoacyl-CCA terminus of tRNA, although the processes these molecules function in are different. These findings reinforced the 'molecular mimicry' or 'tRNA mimicry' hypothesis. Since then, the RF-tRNA mimicry hypothesis has played a crucial role to elucidate the mechanism of translation termination. In the past decade, the crystal structure of the translation termination complex between the ribosome and RFs has been determined at atomic resolution. Overall, the structural data strongly support the RF-tRNA mimicry hypothesis, with shared as well as distinct ribosomal conformations induced by RF or tRNA binding. In this review, we re-evaluate the structural data from the genetic and biochemical viewpoint as our initial functional evidence were not fully interpreted in the previous reports. Recent structural and functional studies of the translation machinery have uncovered that the concept of tRNA mimicry can be expanded for factors beyond translation termination and into translation initiation, elongation, as well as mRNA surveillance pathways for protein synthesis. WIREs RNA 2011 2 647-668 DOI: 10.1002/wrna.81 For further resources related to this article, please visit the WIREs website.
Copyright © 2011 John Wiley & Sons, Ltd.