miR-127-5p targets the 3'UTR of human β-F1-ATPase mRNA and inhibits its translation.

The mitochondrial H(+)-ATP synthase is a bottleneck component in the provision of metabolic energy by oxidative phosphorylation. The expression of its catalytic subunit (β-F1-ATPase) is stringently controlled at post-transcriptional levels during oncogenesis, the cell cycle and in development. Here we show that miR-127-5p targets the 3'UTR of β-F1-ATPase mRNA (β-mRNA) significantly reducing its translational efficiency without affecting β-mRNA abundance. Despite the reduced expression of β-F1-ATPase in most human carcinomas, we observed no expression of miR-127-5p in different human cancer cell lines, minimizing the potential role of miR-127-5p as a regulator of the bioenergetic activity of mitochondria in cancer. In contrast, miR-127-5p is highly over-expressed in the human fetal liver. Consistent with previous findings in the rat, the expression of β-F1-ATPase in the human liver also seems to be controlled at post-transcriptional levels during development, what might suggest a role for miR-127-5p in controlling β-mRNA translation and thus in defining the bioenergetic activity of human liver mitochondria. Moreover, immunolocalization techniques and subcellular fractionation experiments using different antibodies against β-F1-ATPase reveal that the ectopic expression of β-F1-ATPase at the cell surface of the hepatocytes and HepG2 cells is negligible or stands for scrutiny.