Analysis of the enzymatic mechanism of chain extension during protein synthesis and studies with N-formylmethionyl-sRNA suggest that chain initiation requires formylation of the amino group of the amino acid destined to start chain growth. The existence of a set of starting triplets coding for a special set of N-formylaminoacyl-sRNA's is postulated. These triplets might be ambiguous in the sense that they specify different amino acids, depending on whether they are at the beginning of or within a message. A number of starting triplets and their NH(2)-terminal amino acids are predicted from previously suggested ambiguities. The biochenmical, regulatory, and genetic implications of a formylation step controlling chain initiation are discussed.
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