MettRNAfMet

Formylmethionyl-tRNAfMet, commonly abbreviated fMet-tRNAfMet, is the initiator tRNA used to start protein synthesis in most bacteria and in the translation systems of mitochondria and plastids. It carries methionine that has been formylated at the amino terminus. The anticodon CAU of tRNAfMet base-pairs with the start codon AUG in the ribosomal P site, enabling the ribosome to recognize the proper initiation site.

Biochemical formation and role in initiation: Methionine is first charged onto tRNAfMet by methionyl-tRNA synthetase. The aminoacyl-tRNA is then formylated by methionyl-tRNA formyltransferase, using 5,10-methylenetetrahydrofolate as the formyl donor, to produce fMet-tRNAfMet. The formyl group increases the affinity of the initiator tRNA for initiation factors and the ribosome. During initiation, fMet-tRNAfMet is delivered to the 30S subunit in complex with initiation factors (notably IF2) and GTP; after start codon recognition, the 50S subunit joins to form the 70S initiation complex, and IF2 hydrolyzes GTP to release initiation factors. The fMet-tRNAfMet remains in the P site to begin elongation with the first aminoacyl-tRNA.

Post-initiation processing and variation: The formyl group is typically removed from the nascent chain by peptide deformylase during or after initiation, and, depending on the second residue, the initiating methionine may be removed by methionine aminopeptidase. In many organelles of eukaryotic cells, the use of formylated initiator tRNA reflects their bacterial ancestry, while cytosolic eukaryotic translation uses unformylated Met-tRNAiMet.