ИСТИНА

During the course of mitochondrial evolution the vast majority of protein-coding genes were transferred from the organellar DNA to the nucleus. Nevertheless, several mitochondrial genes are still expressed from mitochondrial DNA. Mitochondrial protein synthesis apparatus is unique and possesses lots of differences from its prokaryotic ancestor. Translation initiation is probably the most peculiar step during protein synthesis in mitochondria. Unlike bacteria, where 3 absolutely essential protein factors (IF1, IF2 & IF3) govern this stage, only orthologues of IF2 and IF3 were found in mitochondria. Due to a low percentage identity between mtIF3 and bacterial IF3, the former couldn’t be identified in several organisms for a long time. Recently, we have shown that Aim23p is a missing mtIF3 in baker’s yeast S. cerevisiae. Sequence alignment shows that Aim23p, like bacterial IF3, contains N-domain and C-domain joined by a flexible linker. Furthermore, Aim23p possesses N- and C-terminal extensions as was previously reported for human mtIF3, although yeast ones are longer. It was shown that neither N- nor C-terminus is crucial for human mtIF3 function in promoting initiation complex formation. However, the C-terminal extension is crucial for dissociation of fMet-tRNA bound in the absence of mRNA. Moreover, both extensions are needed for preventing binding of mtIF3 to the large ribosomal subunit. Even so, there was no experimental evidence on the significance of mtIF3 extensions for mitochondrial function in vivo. Our genetic experiments have revealed that, neither N- nor C-terminus of Aim23p alone is crucial for yeast mitochondrial function. Interestingly, simultaneous deletion of both extensions leads to the same phenotype as in case of the whole AIM23 deletion, suggesting that extensions role in Aim23p functioning could be, at least partially, overlapped. Moreover, we have shown that truncated derivative of Aim23p without both termini more efficiently replaces bacterial IF3 in vivo compare to full-length variant. Altogether, our results suggest that both N- and C-terminal extensions of yeast mitochondrial IF3 evolved in response to changes in mitochondrial translation system.