Decoding mechanism of the stop codons and its versatile functions

The mechanism of translation termination has long been a puzzle. The polypeptide-chain release factor (RF) plays a key role in terminating protein synthesis. Bacteria have two codon specific RFs, RF1 and RF2, to decipher three stop codons. Decades ago, an idea was formulated that RFs may be protein analogs of tRNA. This idea gained substantial support ten years ago by the identification of two classes of crucial RF peptide motifs, Peptide-anticodon and GGQ, in bacteria. These motifs are functionally equivalent to the anticodon and aminoacyl-CCA terminus of tRNA, although they are involved in different step of translation. In eularyotes translation termination is catalyzed by two class of proteins, eRF1 and eRF3. eRF1 recognizes stop codons and hydrolyzes peptidyl-tRNA as a tRNA mimic, while eRF3, an elongation factor 1α (EF-1α) homolog, binds to and stimulates the activity of eRF1. The roles of stop codons are known to be versatile. A number of essential genes with a premature stop codon in their protein coding regions are expressed by bypassing translation termination using the Sec (Selenocystein) insertion, translational frameshifting and so on. Such mechanisms are called translational RECODING (= Reprogrammed genetic decoding). Moreover, in eukaryotes, the premature stop codons in aberrant mRNAs are recognized differently from normal stop codons and trigger the NMD (= Nonsense mediated mRNA decay) system to avoid harmful protein synthesis. The tRNA mimicry proteins provide a clue to elucidate the mechanism of stop codon recognition.

For a variety of life phenomena, including the protein synthesis system that we are researching, the constituent factors have been identified and their roles have been clarified. In recent years, the understanding of life through such "reductionist methods" has made great progress due to the remarkable development of analysis techniques in the field of life science. On the other hand, there is growing attention to life phenomenon elucidation methods using "constructive methods" that attempt to reproduce life phenomena by assembling the necessary elements. We aim to comprehensively understand the fundamental principles of the protein synthesis system that fills the gap between the transcriptome and proteome by applying the molecular genetics methods that we are good at in addition to the conventional research approaches. We are working on research with strong expectations that by developing new research approaches, we can capture life phenomena from a new perspective and even create new values.