Journal
NEUROBIOLOGY OF DISEASE
Volume 69, Issue -, Pages 15-22Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2014.04.017
Keywords
Mitochondrial disorders; Translation inhibitors; Non-coding small chimeric RNA; Mitochondrial encoded proteins
Categories
Funding
- National Institutes of Health [AG027453, NS078758, GM103369]
- ASPET Dalton-Zannoni
- Dept. of Pharmacology & Chemical Biology, University of Pittsburgh, School of Medicine
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Endogenous mitochondrial genes encode critical oxidative phosphorylation components and their mutation results in a set of disorders known collectively as mitochondrial encephalomyopathies. There is intensive interest in modulating mitochondrial function as organelle dysfunction has been associated with numerous disease states. Proteins encoded by the mitochondrial genome cannot be genetically manipulated by current techniques. Here we report the development of a mitochondrial-targeted RNA expression system (mtTRES) utilizing distinct non-coding leader sequences (NCLs) and enabling in vivo expression of small mitochondrial-targeted RNAs. mtTRES expressing small chimeric antisense RNAs was used as translational inhibitors (TLIs) to target endogenous mitochondrial protein expression in vivo. By utilizing chimeric antisense RNA we successfully modulate expression of two mitochondrially-encoded proteins, ATP6 and COXII, and demonstrate the utility of this system in vivo and in human cells. This technique has important and obvious research and clinical implications. (C) 2014 Elsevier Inc. All rights reserved.
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