title: RNase-L regulates the stability of mitochondrial DNA-encoded mRNAs in mouse embryo fibroblasts.
abstract: Accelerated decrease in the levels of mitochondrial DNA-encoded mRNA (mt-mRNA) occurs in neuronal cells exposed either to the excitatory amino acid, glutamate or to the sodium ionophore, monensin, suggesting a role of mitochondrial RNase(s) on the stability of mt-mRNAs. Here we report that in mouse embryo fibroblasts that are devoid of the interferon-regulated RNase, RNase-L, the monensin-induced decrease in the half-life of mt-mRNA was reduced. In monensin (250 nM)-treated RNase-L(+/+) cells the average half-life of mt-mRNA, determined after termination of transcription with actinomycin D, was found to be 3h, whereas in monensin-treated RNase-L(-/-) cells the half-life of mt-mRNA was >6h. In contrast, the stability of nuclear DNA-encoded beta-actin mRNA was unaffected. Induction of RNase-L expression in mouse 3T3 fibroblasts further decreased the monensin-induced reduction in mt-mRNA half-life to 1.5h. The results indicate that the RNase-L-dependent decrease in mtDNA-encoded mRNA transcript levels occurs through a decrease in the half-life of mt-mRNA, and that RNase-L may play a role in the stability of mt-mRNA.
authors.affiliation: Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA. kchandra@anethlab.umm.edu
authors.forename: Krish
authors.initials: K
authors.lastname: Chandrasekaran
authors.forename: Zara
authors.initials: Z
authors.lastname: Mehrabian
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Li
authors.forename: Bret
authors.initials: B
authors.lastname: Hassel
mesh_terms: D016475:3T3 Cells; D000818:Animals; D004272:DNA, Mitochondrial / Q000235:genetics*; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology*; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007476:Ionophores / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D008985:Monensin / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000502:physiology; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*
chemical_list: D004272:DNA, Mitochondrial; D007476:Ionophores; D012333:RNA, Messenger; D008985:Monensin; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease