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PMID:29617655
| Citation |
Perks, KL, Rossetti, G, Kuznetsova, I, Hughes, LA, Ermer, JA, Ferreira, N, Busch, JD, Rudler, DL, Spahr, H, Schöndorf, T, Shearwood, AJ, Viola, HM, Siira, SJ, Hool, LC, Milenkovic, D, Larsson, NG, Rackham, O and Filipovska, A (2018) PTCD1 Is Required for 16S rRNA Maturation Complex Stability and Mitochondrial Ribosome Assembly. Cell Rep 23:127-142 |
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| Abstract |
The regulation of mitochondrial RNA life cycles and their roles in ribosome biogenesis and energy metabolism are not fully understood. We used CRISPR/Cas9 to generate heart- and skeletal-muscle-specific knockout mice of the pentatricopeptide repeat domain protein 1, PTCD1, and show that its loss leads to severe cardiomyopathy and premature death. Our detailed transcriptome-wide and functional analyses of these mice enabled us to identify the molecular role of PTCD1 as a 16S rRNA-binding protein essential for its stability, pseudouridylation, and correct biogenesis of the mitochondrial large ribosomal subunit. We show that impaired mitoribosome biogenesis can have retrograde signaling effects on nuclear gene expression through the transcriptional activation of the mTOR pathway and upregulation of cytoplasmic protein synthesis and pro-survival factors in the absence of mitochondrial translation. Taken together, our data show that impaired assembly of the mitoribosome exerts its consequences via differential regulation of mitochondrial and cytoplasmic protein synthesis. |
| Links |
PubMed Online version:10.1016/j.celrep.2018.03.033 |
| Keywords |
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Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| GO:0032543: mitochondrial translation |
ECO:0000315: |
P |
In this paper, they measured de novo mitochondrial protein synthesis of the 13 mtDNA-encoded respiratory complex subunits and showed a dramatic loss of translation in the Ptcd1 knockout mice compared to controls in both tissues (Figures 3A and S1A), indicating that PTCD1 is essential for mitochondrial protein synthesis. |
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Notes
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