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

Initiation factor 3 (IF3) is a conserved translation factor. Mutations in mitochondrial IF3 (IF3_mt) have been implicated in disease pathology. Escherichia coli infCΔ55, compromised for IF3 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.