Activity and Function in Human Cells of the Evolutionary Conserved Exonuclease Polynucleotide Phosphorylase

Falchi, Federica A.; Pizzoccheri, Roberto; Briani, Federica

doi:10.3390/ijms23031652

Cited by 8 publications

(9 citation statements)

References 131 publications

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“…Pnpt1 is evolutionarily conserved and has several well described mitochondrial functions (46). Increased mt-ROS and increased OCR and ECAR were expected in Pnpt1 depleted cells.…”

Section: Discussionmentioning

confidence: 99%

Pnpt1 mediates NLRP3 inflammasome activation by MAVS and metabolic reprogramming in macrophages

Hsu

Sowden

et al. 2022

Preprint

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Polyribonucleotide nucleotidyltransferase 1 (Pnpt1) plays critical roles in mitochondrial homeostasis by controlling mitochondrial RNA (mt-RNA) processing, trafficking and degradation. Pnpt1 deficiency results in mitochondrial dysfunction that triggers a Type I interferon response, suggesting a role in inflammation. However, the role of Pnpt1 in inflammasome activation remains largely unknown. In this study, we generated myeloid-specific Pnpt1-knockout mice, and demonstrated that Pnpt1 depletion enhanced interleukin-1 beta (IL-1β) and interleukin-18 (IL-18) secretion in mouse sepsis models. Using cultured peritoneal and bone marrow-derived macrophages we demonstrated that Pnpt1 regulated NLRP3 inflammasome dependent IL-1β release in response to lipopolysaccharides (LPS), followed by nigericin, ATP or poly (I:C) treatment. Pnpt1 deficiency in macrophages increased glycolysis after LPS, and mt-reactive oxygen species (mt-ROS) after NLRP3 inflammasome activation. Pnpt1 activation of the inflammasome was dependent on both increased glycolysis and expression of the mitochondrial antiviral-signaling protein (MAVS), but not NF-κB signaling. Collectively, these data strengthen the concept that Pnpt1 is an important mediator of inflammation as shown by activation of the NLRP3 inflammasome in mouse sepsis and cultured macrophages.

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“…Pnpt1 is evolutionarily conserved and has several well described mitochondrial functions (46). Increased mt-ROS and increased OCR and ECAR were expected in Pnpt1 depleted cells.…”

Section: Discussionmentioning

confidence: 99%

Pnpt1 mediates NLRP3 inflammasome activation by MAVS and metabolic reprogramming in macrophages

Hsu

Sowden

et al. 2022

Preprint

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“…Metazoan PNPase monomers are very similar to bacterial ones and contain two RNase PH-like domains, followed by a KH domain and an S1 domain [ 96 ]. In seed plants, the mtPNPase monomers are longer and contain an additional S1 domain at their N-termini, as determined by bioinformatics.…”

Section: Mitochondrial Rnases Involved In Rna Quality Control and Deg...mentioning

confidence: 99%

How RNases Shape Mitochondrial Transcriptomes

Cartalas

Coudray

Gobert

2022

IJMS

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Mitochondria are the power houses of eukaryote cells. These endosymbiotic organelles of prokaryote origin are considered as semi-autonomous since they have retained a genome and fully functional gene expression mechanisms. These pathways are particularly interesting because they combine features inherited from the bacterial ancestor of mitochondria with characteristics that appeared during eukaryote evolution. RNA biology is thus particularly diverse in mitochondria. It involves an unexpectedly vast array of factors, some of which being universal to all mitochondria and others being specific from specific eukaryote clades. Among them, ribonucleases are particularly prominent. They play pivotal functions such as the maturation of transcript ends, RNA degradation and surveillance functions that are required to attain the pool of mature RNAs required to synthesize essential mitochondrial proteins such as respiratory chain proteins. Beyond these functions, mitochondrial ribonucleases are also involved in the maintenance and replication of mitochondrial DNA, and even possibly in the biogenesis of mitochondrial ribosomes. The diversity of mitochondrial RNases is reviewed here, showing for instance how in some cases a bacterial-type enzyme was kept in some eukaryotes, while in other clades, eukaryote specific enzymes were recruited for the same function.

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“…PNPase participates in a wide array of cellular processes, including nucleus-encoded RNA import into mitochondria, the processing and decay of miRNA and mRNA [ 7 ], and the processing of polycistronic mitochondrial transcripts and tRNAs [ 8 ]. Although PNPase was discovered in the 1950s [ 9 ], new functions of this protein have been recently discovered [ 10 , 11 ]. Once synthesized, PNPase is guided to the mitochondrial intermembrane space (IMS) [ 6 , 12 ] by a mitochondrial targeting sequence which is cleaved off upon translocation into the IMS [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

“…Nevertheless, except for ISGF3 (IFN-Stimulated Gene Factor 3) and STAT2/IRF9 (Signal Transducer and Activator of Transcription 2-IFN Regulatory Factor 9) [ 11 ], no other transcription factor has been characterized so far for the PNPT1 promoter, despite the importance of this gene for mitochondrial and cellular function. In this study, we have carried out an exhaustive functional characterization of the PNPT1 promoter and determined the role of two important transcription factors, SP1 and NFYA, for PNPT1 expression.…”

Section: Introductionmentioning

confidence: 99%

SP1 and NFY Regulate the Expression of PNPT1, a Gene Encoding a Mitochondrial Protein Involved in Cancer

Ventura

Revert²,

Revert‐Ros³

et al. 2022

IJMS

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The Polyribonucleotide nucleotidyltransferase 1 gene (PNPT1) encodes polynucleotide phosphorylase (PNPase), a 3′-5′ exoribonuclease involved in mitochondrial RNA degradation and surveillance and RNA import into the mitochondrion. Here, we have characterized the PNPT1 promoter by in silico analysis, luciferase reporter assays, electrophoretic mobility shift assays (EMSA), chromatin immunoprecipitation (ChIP), siRNA-based mRNA silencing and RT-qPCR. We show that the Specificity protein 1 (SP1) transcription factor and Nuclear transcription factor Y (NFY) bind the PNPT1 promoter, and have a relevant role regulating the promoter activity, PNPT1 expression, and mitochondrial activity. We also found in Kaplan–Meier survival curves that a high expression of either PNPase, SP1 or NFY subunit A (NFYA) is associated with a poor prognosis in liver cancer. In summary, our results show the relevance of SP1 and NFY in PNPT1 expression, and point to SP1/NFY and PNPase as possible targets in anti-cancer therapy.

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Activity and Function in Human Cells of the Evolutionary Conserved Exonuclease Polynucleotide Phosphorylase

Cited by 8 publications

References 131 publications

Pnpt1 mediates NLRP3 inflammasome activation by MAVS and metabolic reprogramming in macrophages

Pnpt1 mediates NLRP3 inflammasome activation by MAVS and metabolic reprogramming in macrophages

How RNases Shape Mitochondrial Transcriptomes

SP1 and NFY Regulate the Expression of PNPT1, a Gene Encoding a Mitochondrial Protein Involved in Cancer

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