InitiatortRNA

The initiator tRNA, also written as initiator tRNA, is a specialized transfer RNA that initiates translation by delivering the first amino acid to the start codon on the mRNA. It is distinct from elongator tRNAs in its structure and in how it is recognized by the translation initiation machinery. In all domains of life, the initiator tRNA is required to form the first peptide bond and to set the reading frame for the ribosome.

In bacteria, the initiator tRNA is a methionyl tRNA charged with methionine and then formylated to form fMet-tRNAi^fMet. This formylated tRNA preferentially pairs with the start codon AUG in concert with initiation factors IF1, IF2, and IF3 and the small ribosomal subunit. After start codon recognition and subunit joining to form the 70S initiation complex, the formyl group is removed by deformylase, and methionine may be excised from the N-terminus by methionine aminopeptidase depending on the following residue during early elongation.

In eukaryotes and archaea, the initiator tRNA is Met-tRNAi^Met and is not formylated. It works with initiation factors such as eIF2 to recruit the initiator tRNA to the small ribosomal subunit, which then scans the mRNA for an AUG start codon in a favorable context. Once initiation is complete and the 60S subunit joins, Met-tRNAi^Met typically remains in the P site to initiate the polypeptide, and, in many cases, the initial methionine is removed later in processing.

Identity elements and modifications of the initiator tRNA distinguish it from elongator tRNAs and ensure correct recognition by initiation factors and ribosomal positioning.