A mitochondria-specific isoform of FASTK is present in mitochondrial RNA granules and regulates gene expression and function

Cell Rep. 2015 Feb 24;10(7):1110-21. doi: 10.1016/j.celrep.2015.01.063. Epub 2015 Feb 19.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Cell Line
  • Electron Transport Complex I / metabolism
  • Endoribonucleases / metabolism
  • Gene Expression Regulation
  • Humans
  • Mice
  • Microscopy, Confocal
  • Mitochondria / metabolism*
  • Multienzyme Complexes / metabolism
  • Myocardium / metabolism
  • NADH Dehydrogenase / genetics
  • NADH Dehydrogenase / metabolism
  • Polyribonucleotide Nucleotidyltransferase / metabolism
  • Protein Serine-Threonine Kinases / antagonists & inhibitors
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Protein Structure, Tertiary
  • RNA / metabolism*
  • RNA Helicases / metabolism
  • RNA Interference
  • RNA, Messenger / metabolism
  • RNA, Mitochondrial
  • RNA, Small Interfering / metabolism
  • Signal Transduction


  • 3' Untranslated Regions
  • Multienzyme Complexes
  • RNA, Messenger
  • RNA, Mitochondrial
  • RNA, Small Interfering
  • degradosome
  • RNA
  • MT-ND6 protein, human
  • NADH Dehydrogenase
  • FASTK protein, human
  • Protein Serine-Threonine Kinases
  • Polyribonucleotide Nucleotidyltransferase
  • Endoribonucleases
  • RNA Helicases
  • Electron Transport Complex I