Defects of mitochondrial RNA turnover lead to the accumulation of double-stranded RNA in vivo

• Published in: PLoS genetics Vol. 15; no. 7; p. e1008240
• Main Authors: Pajak, Aleksandra, Laine, Isabelle, Clemente, Paula, El-Fissi, Najla, Schober, Florian A., Maffezzini, Camilla, Calvo-Garrido, Javier, Wibom, Rolf, Filograna, Roberta, Dhir, Ashish, Wedell, Anna, Freyer, Christoph, Wredenberg, Anna
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.07.2019; Public Library of Science (PLoS)
• Subjects: Aging; Animals; Antisense RNA; Biochemistry; Biology; Biology and Life Sciences; Biophysics; CRISPR; Cytoplasm; DEAD-box RNA Helicases - genetics; DEAD-box RNA Helicases - metabolism; Deoxyribonucleic acid; DNA; DNA helicase; DNA-Directed RNA Polymerases - genetics; DNA-Directed RNA Polymerases - metabolism; Double-stranded RNA; Drosophila melanogaster - genetics; Drosophila melanogaster - metabolism; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Female; Gene expression; Genetic research; Genomes; Helicases; Hospitals; Insects; Laboratories; Male; Mammals; Medicine; Metabolic disorders; Mitochondria; Mitochondrial DNA; Molecular modelling; Molecular structure; mRNA stability; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Phosphorylase; Phosphorylases; Physiology; Poly(A); Polyadenylation; Polynucleotide adenylyltransferase; Polynucleotide phosphorylase; Polyribonucleotide Nucleotidyltransferase - genetics; Polyribonucleotide Nucleotidyltransferase - metabolism; Research and analysis methods; RNA helicase; RNA interference; RNA Stability; RNA, Antisense - chemistry; RNA, Antisense - metabolism; RNA, Double-Stranded - chemistry; RNA, Double-Stranded - metabolism; RNA, Mitochondrial - chemistry; RNA, Mitochondrial - metabolism; Structure; Supervision; Surgery; Transcription; Sweden
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1008240

The RNA helicase SUV3 and the polynucleotide phosphorylase PNPase are involved in the degradation of mitochondrial mRNAs but their roles in vivo are not fully understood. Additionally, upstream processes, such as transcript maturation, have been linked to some of these factors, suggesting either dual roles or tightly interconnected mechanisms of mitochondrial RNA metabolism. To get a better understanding of the turn-over of mitochondrial RNAs in vivo, we manipulated the mitochondrial mRNA degrading complex in Drosophila melanogaster models and studied the molecular consequences. Additionally, we investigated if and how these factors interact with the mitochondrial poly(A) polymerase, MTPAP, as well as with the mitochondrial mRNA stabilising factor, LRPPRC. Our results demonstrate a tight interdependency of mitochondrial mRNA stability, polyadenylation and the removal of antisense RNA. Furthermore, disruption of degradation, as well as polyadenylation, leads to the accumulation of double-stranded RNAs, and their escape out into the cytoplasm is associated with an altered immune-response in flies. Together our results suggest a highly organised and inter-dependable regulation of mitochondrial RNA metabolism with far reaching consequences on cellular physiology.