PNPASE regulates RNA import into mitochondria.
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.
Wang
Geng
G
Department of Chemistry and Biochemistry, University of California at Los Angeles, Los Angeles, CA 90095, USA.
Chen
Hsiao-Wen
HW
Oktay
Yavuz
Y
Zhang
Jin
J
Allen
Eric L
EL
Smith
Geoffrey M
GM
Fan
Kelly C
KC
Hong
Jason S
JS
French
Samuel W
SW
McCaffery
J Michael
JM
Lightowlers
Robert N
RN
Morse
Herbert C
HC
Koehler
Carla M
CM
Teitell
Michael A
MA
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
D012313:RNA; D011117:Polyribonucleotide Nucleotidyltransferase; D043262:Ribonuclease P