Initiation of Polypeptide
The initiation of polypeptide chain is always brought about by the amino acid methionine, which is regularly coded by the codon AUG, but rarely also by GUG as the initiating codon (consult The Genetic Code). Very rarely initiation may also be directed by UUG (~1%) or AUU (only one case reported). In E. coli, there are two tRNAs for methionine, tRNA_m^met (non-formylatable) and iRNA_f^met (formylatable). The methionine molecule carried by tRNA_m^met cannot be formylated, while that carried by tRNA_f^met can be formylated. In prokaryotes, formylation of initiating amino acid methionine is essential requirement, so that tRNA_f^metis meant for depositing methionine as the first amino acid, while tRNA_m^met deposits methionine at the intercalary positions only. In eukaryotes, formylation of initiating methionine is not brought about due to the absence of tRNA_f^met in plants and due to the absence of enzyme transformylase in animals. Initiation in higher organisms will, therefore, take place without formylation. Differences between prokaryotes and eukaryotes in the mechanisms of initiation of translation are summarized in Table 34.1.