title: miR-127-5p targets the 3'UTR of human β-F1-ATPase mRNA and inhibits its translation.
abstract: 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.
authors.affiliation: Departamento de Biología Molecular, Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, Instituto de Investigación Hospital 12 de Octubre, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
authors.forename: Imke M
authors.initials: IM
authors.lastname: Willers
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Martínez-Reyes
authors.forename: Marta
authors.initials: M
authors.lastname: Martínez-Diez
authors.forename: José M
authors.initials: JM
authors.lastname: Cuezva
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000201:enzymology / Q000648:ultrastructure; D005333:Fetus / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000378:metabolism; D022781:Hepatocytes / Q000201:enzymology / Q000648:ultrastructure; D006801:Humans; D008099:Liver / Q000196:embryology / Q000378:metabolism / Q000648:ultrastructure; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D025261:Mitochondrial Proton-Translocating ATPases / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats
chemical_list: D020413:3' Untranslated Regions; C506526:ATP5F1B protein, human; C547276:MIRN127 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D049452:Green Fluorescent Proteins; D025261:Mitochondrial Proton-Translocating ATPases