Cell - PNPASE Regulates RNA Import into Mitochondria

PNPASE Regulates RNA Import into Mitochondria
Cell, Volume 142, Issue 3, 456-467, 6 August 2010
Copyright 2010 Elsevier Inc. All rights reserved.
10.1016/j.cell.2010.06.035

Referred to by: Mitochondrial Matrix Reloaded with RNA

Authors
Geng Wang, Hsiao-Wen Chen, Yavuz Oktay, Jin Zhang, Eric L. Allen, Geoffrey M. Smith, Kelly C. Fan, Jason S. Hong, Samuel W. French, J. Michael McCaffery, Robert N. Lightowlers, Herbert C. Morse, Carla M. Koehler, Michael A. TeitellSee AffiliationsHint: Rollover Authors and Affiliations Department of Chemistry and Biochemistry, University of California at Los Angeles, Los Angeles, CA 90095, USA Molecular Biology Institute, University of California at Los Angeles, Los Angeles, CA 90095, USA 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 Center for Molecular and Mitochondrial Medicine and Genetics, University of California at Irvine, Irvine, CA 92697, USA Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA Integrated Imaging Center, Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA Mitochondrial Research Group, Institute for Ageing and Health, Newcastle University, Newcastle upon the Tyne, UK Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA Corresponding author

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 PNPASEimported 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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