Fidelity of translation in the presence of mammalian mitochondrial initiation factor 3

Initiation factor 3 (IF3(mt)) is a conserved translation factor. Mutations in mitochondrial IF3(mt) (IF3(mt)) have been implicated in disease pathology. Escherichia coli infC Delta 655, compromised for IF3(mt) activity, has provided an excellent heterologous system for IF3(mt) structure-function analysis. IF3(mt) allowed promiscuous initiation from AUA, AUU and ACG codons but avoided initiation with initiator tRNAs lacking the conserved 3GC pairs in their anticodon stems. Expression of IF3(mt) N-terminal domain, or IF3(mt) devoid of its typical N-, and C-terminal extensions improved fidelity of initiation in E. coli. The observations suggest that the IF3(mt) terminal extensions relax the fidelity of translational initiation in mitochondria.