fMettRNAfMet

fMettRNAfMet, short for formylmethionyl-tRNAfMet, is the initiator tRNA used in bacterial cytoplasmic translation and in some organelles to deliver the N-formylmethionine residue to the ribosome at the start of protein synthesis. The tRNA is charged with methionine by methionyl-tRNA synthetase to form Met-tRNAfMet, and a formyl group is added by the enzyme methionyl-tRNA formyltransferase (FMT) from N10-formyltetrahydrofolate. The resulting formylmethionyl-tRNAfMet is specifically recognized by initiation factors and the ribosome during the formation of the initiation complex.

In bacterial translation, fMet-tRNAfMet participates in the initiation process by pairing with the start codon, typically AUG, and by interacting with initiation factors such as IF1 and IF2, with IF2 acting as a GTPase to deliver the initiator tRNA to the P site of the ribosome. The formyl group on fMet helps discriminate the initiator tRNA from elongator tRNAs, contributing to accurate start site selection. After initiation, the formyl group is usually removed by peptide deformylase, and the nascent polypeptide begins with methionine that is subsequently processed as needed.

Compared with bacteria, eukaryotes and archaea use an unformylated initiator tRNA (Met-tRNAiMet) and different initiation factors (eukaryotic initiation factors instead of IF1/IF2/IF3). Some organelles, such as plastids and certain mitochondria, retain formylation-dependent initiation strategies similar to bacteria. Overall, fMettRNAfMet is a key component of the bacterial translation initiation system.