title: PNPASE regulates RNA import into mitochondria.
abstract: 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.
authors.affiliation: Department of Chemistry and Biochemistry, University of California at Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Geng
authors.initials: G
authors.lastname: Wang
authors.forename: Hsiao-Wen
authors.initials: HW
authors.lastname: Chen
authors.forename: Yavuz
authors.initials: Y
authors.lastname: Oktay
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.forename: Eric L
authors.initials: EL
authors.lastname: Allen
authors.forename: Geoffrey M
authors.initials: GM
authors.lastname: Smith
authors.forename: Kelly C
authors.initials: KC
authors.lastname: Fan
authors.forename: Jason S
authors.initials: JS
authors.lastname: Hong
authors.forename: Samuel W
authors.initials: SW
authors.lastname: French
authors.forename: J Michael
authors.initials: JM
authors.lastname: McCaffery
authors.forename: Robert N
authors.initials: RN
authors.lastname: Lightowlers
authors.forename: Herbert C
authors.initials: HC
authors.lastname: Morse
authors.forename: Carla M
authors.initials: CM
authors.lastname: Koehler
authors.forename: Michael A
authors.initials: MA
authors.lastname: Teitell
mesh_terms: D000818:Animals; D002460:Cell Line; D055786:Gene Knockout Techniques; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism*; D011117:Polyribonucleotide Nucleotidyltransferase / Q000235:genetics / Q000378:metabolism*; D012313:RNA / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D043262:Ribonuclease P / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism
chemical_list: D012313:RNA; D011117:Polyribonucleotide Nucleotidyltransferase; D043262:Ribonuclease P