Protein That Shuttles RNA Into Cell Mitochondria Discovered
ScienceDaily (Aug. 8, 2010) — Researchers at UCLA's Jonsson Comprehensive Cancer Center and the departments of Chemistry and Biochemistry and Pathology and Laboratory Medicine have uncovered a role for an essential cell protein in shuttling RNA into the mitochondria, the energy-producing "power plant" of the cell.
Researchers at UCLA's Jonsson Comprehensive Cancer Center and the departments of Chemistry and Biochemistry and Pathology and Laboratory Medicine have uncovered a role for an essential cell protein in shuttling RNA into the mitochondria, the energy-producing "power plant" of the cell. (Credit: Maureen Heaster)
In the current study, UCLA scientists show a new role for a protein called polynucleotide phosphorylase (PNPASE) in regulating the import of RNA into mitochondria. Reducing the expression of PNPASE decreased RNA import, which impaired the processing of mitochondrial genome-encoded RNAs. Reduced RNA processing inhibited the translation of proteins required to maintain the electron transport chain that handles oxygen to produce energy in the form of adenosine triphosphate, the energy currency of a cell. With reduced PNPASE, unprocessed mitochondrial RNAs accumulated, protein translation was inhibited and energy production was compromised, leading to stalled cell growth.
The study appears Aug. 5, 2010, in the peer-reviewed journalCell.
"This discovery tells us that PNPASE regulates the energy producing function of mitochondria by mediating cytoplasmic RNA import," said Dr. Michael Teitell, a professor of pathology and laboratory medicine, a Jonsson Cancer Center researcher and co-senior author of the study. "The study yields new insight for how cells function at a very fundamental level. This information provides a potential new pathway to control mitochondrial energy production and possibly impact the growth of cells, including certain types of cancer cells."
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doi:10.1016/j.cell.2010.06.035
PNPASE Regulates RNA Import into Mitochondria
Geng Wang1, Hsiao-Wen Chen4, Yavuz Oktay1, Jin Zhang5, Eric L. Allen5, Geoffrey M. Smith5, Kelly C. Fan5, Jason S. Hong5, Samuel W. French5, J. Michael McCaffery6, Robert N. Lightowlers7, Herbert C. Morse8, Carla M. Koehler1, 2, , and Michael A. Teitell2, 3, 5, ,
1 Department of Chemistry and Biochemistry, University of California at Los Angeles, Los Angeles, CA 90095, USA
2 Molecular Biology Institute, University of California at Los Angeles, Los Angeles, CA 90095, USA
3 Jonsson Comprehensive Cancer Center, Broad Stem Cell Research Center, California NanoSystems Institute, and Center for Cell Control, University of California at Los Angeles, Los Angeles, CA 90095, USA
4 Center for Molecular and Mitochondrial Medicine and Genetics, University of California at Irvine, Irvine, CA 92697, USA
5 Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
6 Integrated Imaging Center, Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA
7 Mitochondrial Research Group, Institute for Ageing and Health, Newcastle University, Newcastle upon the Tyne, UK
8 Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA
Graphical abstract
Highlights► PNPASE reduction inhibits mitochondrial RNA processing, translation, and respiration ► PNPASE imports the RNA components of RNase P and MRP RNases, 5S rRNA, and tRNAs into mitochondria ► The RNA import activity of PNPASE is separable from its RNA processing activity ► A transferrable 20 nt stem-loop structure mediates PNPASE-dependent import of RNase P and MRP RNAs
Summary
RNA import into mammalian mitochondria is considered essential for replication, transcription, and translation of the mitochondrial genome but the pathway(s) and factors that control this import are poorly understood. Previously, we localized polynucleotide phosphorylase (PNPASE), a 3′ → 5′ exoribonuclease and poly-A polymerase, in the mitochondrial intermembrane space, a location lacking resident RNAs. Here, we show a new role for PNPASE in regulating the import of nuclear-encoded RNAs into the mitochondrial matrix. PNPASE reduction impaired mitochondrial RNA processing and polycistronic transcripts accumulated. Augmented import of RNase P, 5S rRNA, and MRP RNAs depended on PNPASE expression and PNPASE–imported RNA interactions were identified. PNPASE RNA processing and import activities were separable and a mitochondrial RNA targeting signal was isolated that enabled RNA import in a PNPASE-dependent manner. Combined, these data strongly support an unanticipated role for PNPASE in mediating the translocation of RNAs into mitochondria.
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