title: A mitochondria-specific isoform of FASTK is present in mitochondrial RNA granules and regulates gene expression and function.
abstract: The mitochondrial genome relies heavily on post-transcriptional events for its proper expression, and misregulation of this process can cause mitochondrial genetic diseases in humans. Here, we report that a novel translational variant of Fas-activated serine/threonine kinase (FASTK) co-localizes with mitochondrial RNA granules and is required for the biogenesis of ND6 mRNA, a mitochondrial-encoded subunit of the NADH dehydrogenase complex (complex I). We show that ablating FASTK expression in cultured cells and mice results specifically in loss of ND6 mRNA and reduced complex I activity in vivo. FASTK binds at multiple sites along the ND6 mRNA and its precursors and cooperates with the mitochondrial degradosome to ensure regulated ND6 mRNA biogenesis. These data provide insights into the mechanism and control of mitochondrial RNA processing within mitochondrial RNA granules.
authors.affiliation: Department of Cell Biology, University of Geneva, 30 quai Ernest-Ansermet, 1211 Genève 4, Switzerland.
authors.forename: Alexis A
authors.initials: AA
authors.lastname: Jourdain
authors.affiliation: Department of Cell Biology, University of Geneva, 30 quai Ernest-Ansermet, 1211 Genève 4, Switzerland.
authors.forename: Mirko
authors.initials: M
authors.lastname: Koppen
authors.affiliation: Department of Cell Biology, University of Geneva, 30 quai Ernest-Ansermet, 1211 Genève 4, Switzerland.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Rodley
authors.affiliation: Department of Cell Biology, University of Geneva, 30 quai Ernest-Ansermet, 1211 Genève 4, Switzerland.
authors.forename: Kinsey
authors.initials: K
authors.lastname: Maundrell
authors.affiliation: UMR CNRS 6214 - INSERM 1083, Département de Biochimie et Génétique, CHU d'Angers, 4 rue Larrey, 49933 Angers Cedex, France.
authors.forename: Naïg
authors.initials: N
authors.lastname: Gueguen
authors.affiliation: UMR CNRS 6214 - INSERM 1083, Département de Biochimie et Génétique, CHU d'Angers, 4 rue Larrey, 49933 Angers Cedex, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Reynier
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III, Melchor Fernández Almagro 3, 28029 Madrid, Spain.
authors.forename: Adela M
authors.initials: AM
authors.lastname: Guaras
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III, Melchor Fernández Almagro 3, 28029 Madrid, Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: Enriquez
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, One Jimmy Fund Way, Smith 652, Boston, MA 02115, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Anderson
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, One Jimmy Fund Way, Smith 652, Boston, MA 02115, USA; Departamento de Microbiologia, Facultad de Medicina, Edificio de Ciencias de la Salud, Avda ramon y Cajal 7, Valladolid 47005, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Simarro
authors.affiliation: Department of Cell Biology, University of Geneva, 30 quai Ernest-Ansermet, 1211 Genève 4, Switzerland. Electronic address: jean-claude.martinou@unige.ch.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Martinou
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D002460:Cell Line; D042967:Electron Transport Complex I / Q000378:metabolism; D004722:Endoribonucleases / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009245:NADH Dehydrogenase / Q000235:genetics / Q000378:metabolism; D011117:Polyribonucleotide Nucleotidyltransferase / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012313:RNA / Q000378:metabolism*; D020365:RNA Helicases / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D000077278:RNA, Mitochondrial; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D020413:3' Untranslated Regions; D009097:Multienzyme Complexes; D012333:RNA, Messenger; D000077278:RNA, Mitochondrial; D034741:RNA, Small Interfering; C111244:degradosome; D012313:RNA; C507225:MT-ND6 protein, human; D009245:NADH Dehydrogenase; C095367:FASTK protein, human; D017346:Protein Serine-Threonine Kinases; D011117:Polyribonucleotide Nucleotidyltransferase; D004722:Endoribonucleases; D020365:RNA Helicases; D042967:Electron Transport Complex I