title: Drosophila melanogaster LRPPRC2 is involved in coordination of mitochondrial translation.
abstract: Members of the pentatricopeptide repeat domain (PPR) protein family bind RNA and are important for post-transcriptional control of organelle gene expression in unicellular eukaryotes, metazoans and plants. They also have a role in human pathology, as mutations in the leucine-rich PPR-containing (LRPPRC) gene cause severe neurodegeneration. We have previously shown that the mammalian LRPPRC protein and its Drosophila melanogaster homolog DmLRPPRC1 (also known as bicoid stability factor) are necessary for mitochondrial translation by controlling stability and polyadenylation of mRNAs. We here report characterization of DmLRPPRC2, a second fruit fly homolog of LRPPRC, and show that it has a predominant mitochondrial localization and interacts with a stem-loop interacting RNA binding protein (DmSLIRP2). Ubiquitous downregulation of DmLrpprc2 expression causes respiratory chain dysfunction, developmental delay and shortened lifespan. Unexpectedly, decreased DmLRPPRC2 expression does not globally affect steady-state levels or polyadenylation of mitochondrial transcripts. However, some mitochondrial transcripts abnormally associate with the mitochondrial ribosomes and some products are dramatically overproduced and other ones decreased, which, in turn, results in severe deficiency of respiratory chain complexes. The function of DmLRPPRC2 thus seems to be to ensure that mitochondrial transcripts are presented to the mitochondrial ribosomes in an orderly fashion to avoid poorly coordinated translation.
authors.affiliation: Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, Cologne 50931, Germany.
authors.forename: Francesca
authors.initials: F
authors.lastname: Baggio
authors.affiliation: Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, Cologne 50931, Germany.
authors.forename: Ana
authors.initials: A
authors.lastname: Bratic
authors.affiliation: Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, Cologne 50931, Germany.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Mourier
authors.affiliation: Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, Cologne 50931, Germany.
authors.forename: Timo E S
authors.initials: TE
authors.lastname: Kauppila
authors.affiliation: Department of the Biological Mechanisms of Ageing, Max Planck Institute for Biology of Ageing, Cologne 50931, Germany.
authors.forename: Luke S
authors.initials: LS
authors.lastname: Tain
authors.affiliation: Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, Cologne 50931, Germany FACS & Imaging Core Facility, Max Planck Institute for Biology of Ageing, Cologne 50931, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Kukat
authors.affiliation: Department of Computational Biology, Max Planck Institute of Biochemistry, Martinsried 82152, Germany.
authors.forename: Bianca
authors.initials: B
authors.lastname: Habermann
authors.affiliation: Department of the Biological Mechanisms of Ageing, Max Planck Institute for Biology of Ageing, Cologne 50931, Germany.
authors.forename: Linda
authors.initials: L
authors.lastname: Partridge
authors.affiliation: Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, Cologne 50931, Germany Department of Laboratory Medicine, Karolinska Institutet, Stockholm 17177, Sweden larsson@age.mpg.de.
authors.forename: Nils-Göran
authors.initials: NG
authors.lastname: Larsson
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D004579:Electron Transport; D008136:Longevity; D008928:Mitochondria / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D026723:Polyadenylation; D014176:Protein Biosynthesis; D012313:RNA / Q000378:metabolism; D034622:RNA Interference; D000077278:RNA, Mitochondrial; D014158:Transcription, Genetic
chemical_list: D029721:Drosophila Proteins; C000597605:LRPPRC2 protein, Drosophila; D024101:Mitochondrial Proteins; D000077278:RNA, Mitochondrial; D012313:RNA