tRNAfMet

tRNAfMet, or formylmethionine tRNA, is a specialized transfer RNA used to initiate protein synthesis in most bacteria and in organelles with a bacterial-type translation system, such as mitochondria and chloroplasts. It carries a methionine residue that is subsequently formylated, producing N-formylmethionine (fMet) that serves as the initiating amino acid for nascent polypeptides. In contrast, cytosolic translation in most eukaryotes begins with methionine that is not formylated.

The tRNA is first charged with methionine by methionyl-tRNA synthetase. The charged Met-tRNA is then converted to its formylated form by methionyl-tRNA formyltransferase, yielding fMet-tRNAi^Met. This formyl group is recognized by the ribosome and initiation factors, helping to direct the tRNA to the start codon. In bacteria, initiation factors, particularly IF-2, cooperate with fMet-tRNAi^Met and the 30S ribosomal subunit to assemble the initiation complex at AUG start codons, and occasionally at alternative start codons such as GUG.

The formyl group is usually removed after initiation by peptide deformylase as the nascent chain elongates, and subsequent processing may modify the N-terminus further. tRNAfMet is structurally distinct from elongator tRNAMet, enabling specific recognition by initiation machinery and preventing premature accommodation at internal AUG codons.

In summary, tRNAfMet functions as the initiator tRNA in bacterial and organellar translation, supplying the first amino acid in the formylated state and guiding proper initiation of protein synthesis.