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

Abstract Initiation factor 3 (IF3) is a conserved translation factor. Mutations in mitochondrial IF3 (IF3 mt ) have been implicated in disease pathology. Escherichia coli infC Δ55, 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.