RRC ID 32394
Author Baggio F, Bratic A, Mourier A, Kauppila TE, Tain LS, Kukat C, Habermann B, Partridge L, Larsson NG.
Title Drosophila melanogaster LRPPRC2 is involved in coordination of mitochondrial translation.
Journal Nucleic Acids Res
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.
Volume 42(22)
Pages 13920-38
Published 2014-12-16
DOI 10.1093/nar/gku1132
PII gku1132
PMID 25428350
PMC PMC4267620
MeSH Animals Drosophila Proteins / genetics Drosophila Proteins / metabolism Drosophila Proteins / physiology* Drosophila melanogaster / genetics Drosophila melanogaster / growth & development Drosophila melanogaster / metabolism Electron Transport Longevity Mitochondria / genetics* Mitochondrial Proteins / genetics Mitochondrial Proteins / metabolism Mitochondrial Proteins / physiology* Polyadenylation Protein Biosynthesis* RNA / metabolism RNA Interference RNA, Mitochondrial Transcription, Genetic
IF 11.502
Times Cited 12
Drosophila 14786R-2 14786R-4