A mitochondria-specific isoform of FASTK is present in mitochondrial RNA granules and regulates gene expression and function
Résumé
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.
Mots clés
3' Untranslated Regions
Animals
Cell Line
Electron Transport Complex I
Endoribonucleases
Gene Expression Regulation
Humans
Mice
Microscopy
Confocal
mitochondria
Multienzyme Complexes
Myocardium
NADH Dehydrogenase
Polyribonucleotide Nucleotidyltransferase
Protein Structure
Tertiary
Protein-Serine-Threonine Kinases
RNA
RNA Helicases
RNA Interference
Messenger
Mitochondrial
Small Interfering
Signal Transduction