More surprises in translation: initiation without the initiator tRNA

One of the most widespread beliefs in molecular biology is that protein synthesis is initiated with methionine or formylmethionine in all organisms, by using AUG as the initiation codon and a special methionine tRNA called the initiator tRNA (1, 2). Eubacteria, mitochondria, and chloroplasts initiate protein synthesis with formylmethionine, whereas archaebacteria and eukaryotic cytoplasm initiate with methionine. In eubacteria, codons such as GUG and UUG, which are related to AUG by a single base change, are occasionally used for initiation. However, these codons are read by the same initiator tRNA and are, therefore, translated as formylmethionine. In eukaryotic systems, AUG is almost exclusively the codon used for initiation. In the rare cases where ACG, CUG, AUU, and AGG are used, protein synthesis is still thought to be initiated with methionine (3–5).