PNPASE Regulates RNA Import into Mitochondria

Wang, Geng; Chen, Hsiao‐Wen; Oktay, Yavuz; Zhang, Jin; Allen, Eric L.; Smith, George S.; Fan, Kelly C.; Hong, Jason; French, Samuel W.; McCaffery, J. Michael; Lightowlers, Robert N.; Morse, Herbert C.; Koehler, Carla M.; Teitell, Michael A.

doi:10.1016/j.cell.2010.06.035

Cited by 320 publications

(442 citation statements)

References 42 publications

(69 reference statements)

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“…To date, several groups have reported successful examples of mitochondrial RNA delivery [29][30][31], since the fact that the mitochondrion possesses endogenous RNA imported via an RNA signal tag system in these studies [32,33]. Moreover, it has been reported that allotropic expression in the nucleus, followed by the transfer of a signal tag fused protein to the mitochondria appears promising [11].…”

Section: Discussionmentioning

confidence: 99%

Localization of exogenous DNA to mitochondria in skeletal muscle following hydrodynamic limb vein injection

Yasuzaki

Yamada

Kanefuji

et al. 2013

Journal of Controlled Release

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ABSTRACT.Mitochondrial genetic disorders are a major cause of mitochondrial diseases. It is therefore likely that mitochondrial gene therapy will be useful for the treatment of such diseases. Here, we report on the possibility of mitochondrial gene delivery in skeletal muscle using hydrodynamic limb vein (HLV) injection. The HLV injection procedure, a useful method for transgene expression in skeletal muscle, involves the rapid injection of a large volume of naked plasmid DNA (pDNA) into the distal vein of a limb. We hypothesized that the technique could be used to deliver pDNA not only to nuclei but also mitochondria, since cytosolic pDNA that is internalized by the method may be able to overcome mitochondrial membrane. We determined if pDNA could be delivered to myofibrillar mitochondria by HLV injection by PCR analysis. Mitochondrial toxicity assays showed that the HLV injection had no influence on mitochondrial function. These findings indicate that HLV injection promises to be a useful technique for in vivo mitochondrial gene delivery.

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Section: Discussionmentioning

confidence: 99%

Localization of exogenous DNA to mitochondria in skeletal muscle following hydrodynamic limb vein injection

Yasuzaki

Yamada

Kanefuji

et al. 2013

Journal of Controlled Release

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“…First, two recent, independent studies have shown the presence of the RNA subunit of both P and MRP RNases in the matrix of human mitochondria (97,99). Although the corresponding protein subunits have not been found in this organelle, from the protein composition already described, it can be inferred that their function could be performed by a different set of proteins.…”

Section: Exceptions To the Rule: Uncommon Sources For Rnase P/mrp Funmentioning

confidence: 99%

“…This is indeed true in the case of mitochondrial RNase P from yeast, a RNP complex where one protein component is unrelated to the nuclear protein components (100). Moreover, there is evidence that the RNAs imported to the human mitochondria by PNPase are involved, at least to some degree, with tRNA processing (97).…”

Section: Exceptions To the Rule: Uncommon Sources For Rnase P/mrp Funmentioning

confidence: 99%

Ribonucleases P/MRP and the Expanding Ribonucleoprotein World

et al. 2012

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SummaryOne of the hallmarks of life is the widespread use of certain essential ribozymes. The ubiquitous ribonuclease P (RNase P) and eukaryotic RNase MRP are essential complexes where a structured, noncoding RNA acts in catalysis. Recent discoveries have elucidated the three-dimensional structure of the ancestral ribonucleoprotein complex, suggested the possibility of a proteinonly composition in organelles, and even noted the absence of RNase P in a non-free-living organism. With respect to these last two findings, import mechanisms for RNases P/MRP into mitochondria have been demonstrated, and RNase P is present in organisms with some of the smallest known genomes. Together, these results have led to an ongoing debate regarding the precise definition of how ''essential'' these ribozymes truly are. IUBMBIUBMB Life, 64(6): [521][522][523][524][525][526][527][528] 2012

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“…RNase P typically functions as an RNA-protein complex, comprised of one conserved RNA and a varying number of protein subunits, depending on the domain of life: one in Bacteria, at least four in Archaea, and nine or more in the eukaryotic nucleus (4,5). A precedent in which the RNA component is missing entirely is found in human and Arabidopsis organellar RNase P (6, 7), although a recent study suggests the possible coexistence of protein-only and RNA-protein-based RNase P complexes in human mitochondria (8).…”

mentioning

confidence: 99%

Discovery of a minimal form of RNase P in Pyrobaculum

Lai

Chan

Cozen

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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RNase P RNA is an ancient, nearly universal feature of life. As part of the ribonucleoprotein RNase P complex, the RNA component catalyzes essential removal of 5′ leaders in pre-tRNAs. In 2004, Li and Altman computationally identified the RNase P RNA gene in all but three sequenced microbes: Nanoarchaeum equitans, Pyrobaculum aerophilum, and Aquifex aeolicus (all hyperthermophiles) [Li Y, Altman S (2004) RNA 10:1533-1540. A recent study concluded that N. equitans does not have or require RNase P activity because it lacks 5′ tRNA leaders. The "missing" RNase P RNAs in the other two species is perplexing given evidence or predictions that tRNAs are trimmed in both, prompting speculation that they may have developed novel alternatives to 5′ pre-tRNA processing. Using comparative genomics and improved computational methods, we have now identified a radically minimized form of the RNase P RNA in five Pyrobaculum species and the related crenarchaea Caldivirga maquilingensis and Vulcanisaeta distributa, all retaining a conventional catalytic domain, but lacking a recognizable specificity domain. We confirmed 5′ tRNA processing activity by high-throughput RNA sequencing and in vitro biochemical assays. The Pyrobaculum and Caldivirga RNase P RNAs are the smallest naturally occurring form yet discovered to function as trans-acting precursor tRNA-processing ribozymes. Loss of the specificity domain in these RNAs suggests altered substrate specificity and could be a useful model for finding other potential roles of RNase P. This study illustrates an effective combination of next-generation RNA sequencing, computational genomics, and biochemistry to identify a divergent, formerly undetectable variant of an essential noncoding RNA gene.catalytic RNA | gene finding | RNA processing R Nase P is best known for its role in removing the 5′ leaders of pre-tRNAs, an essential step in tRNA maturation. It also processes other RNAs in bacteria and eukaryotes, but these roles are less understood (1-3). RNase P typically functions as an RNA-protein complex, comprised of one conserved RNA and a varying number of protein subunits, depending on the domain of life: one in Bacteria, at least four in Archaea, and nine or more in the eukaryotic nucleus (4, 5). A precedent in which the RNA component is missing entirely is found in human and Arabidopsis organellar RNase P (6, 7), although a recent study suggests the possible coexistence of protein-only and RNA-protein-based RNase P complexes in human mitochondria (8).The inability to identify RNase P in some organisms has sown doubts about whether it is a universal feature of life. Studies of the hyperthermophilic bacterium Aquifex aeolicus showed that it exhibits RNase P-like trimming of tRNAs (9, 10), yet a gene for the expected protein component is absent and the RNA has remained elusive (11), prompting speculation that it may have developed a unique solution for pre-tRNA processing (9). Perhaps most surprisingly, Söll and coworkers (12) demonstrated that the archaeal symbiont Nanoarchaeum equ...

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PNPASE Regulates RNA Import into Mitochondria

Cited by 320 publications

References 42 publications

Localization of exogenous DNA to mitochondria in skeletal muscle following hydrodynamic limb vein injection

Localization of exogenous DNA to mitochondria in skeletal muscle following hydrodynamic limb vein injection

Ribonucleases P/MRP and the Expanding Ribonucleoprotein World

Discovery of a minimal form of RNase P in Pyrobaculum

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