Methods to Transport RNA into Mitochondria

Tech ID: 29970 / UC Case 2009-533-0

Summary

Researchers at UCLA’s Jonsson Comprehensive Cancer Center, the Department of Chemistry and Biochemistry, and the Department of Pathology and Laboratory Medicine have uncovered a role for an essential cell protein, polynucleotide phosphorylase (PNPASE) in shuttling RNA into the mitochondria, the energy-producing “power plant” of the cell. This discovery sets the foundation for the development of long-term nucleic acid-based correction of mitochondrial-encoded defects through stem cells or other treatment vehicles.

Background

The import of nucleus-encoded small RNAs into mitochondria is essential for the replication, transcription and translation of the mitochondrial genome, but little is known about RNA import from the cytoplasm into mitochondria. The mitochondrial genome contains 13 genes that encode for electron transport chain proteins and a number of intervening transfer RNAs (tRNAs) for mitochondrial protein translation. To assist in the process of expressing the mitochondrial genome, which is essential for life and energy production, several nuclear-encoded RNAs must be imported into the mitochondria. Finding the proteins responsible for RNA transport into the nucleus has significant clinical impact, as mitochondrial dysfunction contributes to a broad spectrum of diseases because of defects in energy production, free radical damage, and perturbations in cell life and death pathways.

Innovation

Researchers at UCLA’s Jonsson Comprehensive Cancer Center, the Department of Chemistry and Biochemistry, and the Department of Pathology and Laboratory Medicine have uncovered a novel role for the cell protein polynucleotide phosphorylase (PNPASE) in shuttling RNA into the mitochondria. PNPASE is the first known factor to mediate RNA import into mitochondria. Reducing the expression of PNPASE decreased RNA import, which impaired the processing of mitochondrial genome-encoded RNAs. With reduced PNPASE, energy production was compromised and cell growth was stalled. This discovery sets the foundation for the development of long-term nucleic acid-based correction of mitochondrial-encoded defects through stem cells or other treatment vehicles.

Applications

  • Long-term nucleic acid-based correction of mitochondrial-encoded defects through stem cells or other treatment vehicles 
  • Inhibition of cancer through the development of a PNPASE inhibitor

Advantages

  •          First report of a protein that transports RNA into mitochondria

State Of Development

The role of PNPASE in RNA transport into mitochondria has been published in the peer-reviewed journal Cell. Therapeutic use of the discovery is conceptual.

Related Materials

  • Wang G, Chen HW, Oktay Y, et al. PNPASE regulates RNA import into mitochondria. Cell. 2010;142(3):456-67.

Patent Status

Country Type Number Dated Case
United States Of America Issued Patent 9,238,041 01/19/2016 2009-533
 

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Inventors

  • Teitell, Michael A.

Other Information

Keywords

mitochondria, RNA transport, mitochondrial disease, cell metabolism and energy, cancer

Categorized As

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