Initiator tRNA may recognize more than the initiation codon in mRNA: a model for translational initiation

A special methionine tRNA (tRNAi) is universally required to initiate translation. Amongst species a tRNAi structural conservation is most apparent in the anticodon and T arms of the molecule but extends into the variable loop and the 3' strand of the D stem. This suggested that they could share a similar ancestral or current function in initiation of translation. We report that the sequence of bases neighboring the translational start codons of many eubacterial genes are complementary not only to the extended anticodon but also to the D and T loops of tRNAi. Study of the coding properties of tRNAi and of mutations that affect translation suggests that the translational start domain can be a mosaic of signals complementary to the loops of tRNAi. The hypothesis of multiple loop recognition suggests that unusual triplets can start prokaryotic and mitochondrial genes and predicts the occurrence of other reading frames. Furthermore, it suggests a unifying model for chain initiation based on RNA contacts and displacements.