|
| Status |
Public on May 01, 2018 |
| Title |
PNPase knockout results in mtDNA loss and an altered metabolic gene expression program |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Polynucleotide phosphorylase (PNPase) is an essential mitochondria-localized exoribonuclease implicated in multiple biological processes and several human disorders. To reveal role(s) for PNPase in mitochondria, we established PNPase knockout (PKO) systems by first shifting culture conditions to enable cell growth with defective respiration. PKO resulted in loss of mitochondrial DNA (mtDNA) and a transcriptional profile similar to rho0 mtDNA deleted cells, with perturbations in cholesterol, lipid, and secondary alcohol metabolic pathways. PKO cells also showed growth and cell cycle profiles similar to rho0 cells. PKO in mouse inner ear hair cells cause progressive hearing loss that parallel human familial hearing loss previously linked to mutations in PNPase. Combined, our data suggest that mtDNA maintenance could provide a unifying connection for the large number of biological activities reported for PNPase.
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| Overall design |
Biological triplicate (n = 3) each of Pnpt1 fl/fl mouse embryonic fibroblast (MEF) (TM6), ditercalinium dichloride dihydrochloride treated Pnpt1 fl/fl mtDNA-deficient MEF (rho0), and Pnpt1 fl/fl Adenoviral-Cre treated PNPase KO MEF (PKO) cultures (12 samples total).
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| Contributor(s) |
Ahsan FM, Teitell MA |
| Citation(s) |
30024931 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R01 GM073981 |
RNA trafficking in mitochondria |
UNIVERSITY OF CALIFORNIA LOS ANGELES |
MICHAEL A TEITELL |
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| |
| Submission date |
Mar 12, 2018 |
| Last update date |
Mar 21, 2019 |
| Contact name |
Fasih Mubtasim Ahsan |
| Organization name |
Massachusetts General Hospital
|
| Department |
Center for Genomic Medicine
|
| Lab |
Soukas Lab
|
| Street address |
185 Cambridge Street, CPZN 6500
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02114 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (12)
|
| GSM3036886 |
TM6-1: PNPT1 fl/fl WT (TM6 MEF) Replicate 1 |
| GSM3036887 |
TM6-2: PNPT1 fl/fl WT (TM6 MEF) Replicate 2 |
| GSM3036888 |
TM6-3: PNPT1 fl/fl WT (TM6 MEF) Replicate 3 |
| GSM3036889 |
R0-1: DC-Treated PNPT1 fl/fl (rho0 MEF) Replicate 1 |
| GSM3036890 |
R0-2: DC-Treated PNPT1 fl/fl (rho0 MEF) Replicate 2 |
| GSM3036891 |
R0-3: DC-Treated PNPT1 fl/fl (rho0 MEF) Replicate 3 |
| GSM3036892 |
PK1-1: Ad-Cre PNPT1 fl/fl (PKO MEF) Clone 1 Replicate 1 |
| GSM3036893 |
PK1-2: Ad-Cre PNPT1 fl/fl (PKO MEF) Clone 1Replicate 2 |
| GSM3036894 |
PK1-3: Ad-Cre PNPT1 fl/fl (PKO MEF) Clone 1Replicate 3 |
| GSM3036895 |
PK6-1: Ad-Cre PNPT1 fl/fl (PKO MEF) Clone 6 Replicate 1 |
| GSM3036896 |
PK6-2: Ad-Cre PNPT1 fl/fl (PKO MEF) Clone 6 Replicate 2 |
| GSM3036897 |
PK6-3: Ad-Cre PNPT1 fl/fl (PKO MEF) Clone 6 Replicate 3 |
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| Relations |
| BioProject |
PRJNA437833 |
| SRA |
SRP134850 |
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