VL30 retrotransposition signals activation of a caspase-independent and p53-dependent death pathway associated with mitochondrial and lysosomal damage

Noutsopoulos, Dimitrios; Μαρκόπουλος, Γεώργιος; Vartholomatos, George; Kolettas, Evangelos; Kolaitis, Nicolaos; Tzavaras, Theodore

doi:10.1038/cr.2010.48

Cited by 27 publications

(27 citation statements)

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“…The results showed that Bcl-2 expression was decreased but Bax was increased, suggesting the existence of mitochondrial outer membrane permeabilization (MOMP) during the RRP22-induced cell apoptosis. MOMP, which was previously considered the signal for the caspase pathway, has been identified as the crucial factor for CICD activation [17,18]. Moreover, previous research has revealed that direct induction of MOMP through ectopic Bax expression is sufficient to induce death in the presence of caspase inhibitors [19].…”

Section: Discussionmentioning

confidence: 98%

“…These specimens were obtained from patients who underwent either explorative or radical surgery at Xiangya Hospital (Hunan, China) after informed consent. The astrocytomas were histopathologically and clinically diagnosed at the Xiangya Hospital of Central South University from 2007 to 2010 and classified according to World Health Organization criteria (2007), including grade I (11), grade II (15), grade III (18), and GBMs grade IV (14). For comparisons, five normal brain tissue samples were obtained from patients who were injured in traffic accidents and underwent a decompressive operation.…”

Section: Patient Information and Tissue Specimensmentioning

confidence: 99%

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RRP22: a novel neural tumor suppressor for astrocytoma

et al. 2011

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Astrocytomas are the most common neoplasm of the central nervous system. Although progress has been made, the survival rate of astrocytoma is still poor. Therefore, improving the prognosis of patients with astrocytomas relies on effective therapies that are directed against unique molecular aberrations. Previous studies have revealed that a novel member of the Ras superfamily, RRP22, which is located on chromosome 22 on the 12q site, is exclusively expressed in the central nervous system. RRP22 can be modified by farnesyl and down-regulated in a variety of neural tumor cell lines. In this study, we analyzed the mRNA level of RRP22 in normal brain tissues and astrocytomas using quantitative RT-PCR. Our results showed that the mRNA level in astrocytomas was significantly down-regulated compared to levels in normal tissues. As the pathological grade (World Health Organization (WHO) classification 2007) increased, the expression of RRP22 decreased. However, according to our research, there was no significant difference between malignant astrocytomas with pathological grades of III or IV. To investigate the possible effects of RRP22 on the biological behavior of glioma cells, we transfected RRP22 into a malignant cell line of astrocytomas, U251. We found that RRP22 inhibited growth, decreased invasiveness, and induced cell death. Thus, RRP22 is a special neural tumor suppressor for human astrocytomas, although further studies are needed to define the detailed mechanisms.

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Section: Discussionmentioning

confidence: 98%

Section: Patient Information and Tissue Specimensmentioning

confidence: 99%

RRP22: a novel neural tumor suppressor for astrocytoma

et al. 2011

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“…These results support the hypothesis that the VL30 RNA is imported. The import of VL-30 retroelement RNA is surprising, and the replication of these results and exploration of biological significance of this observation will be important, considering recent research implicating VL30 RNA with mitochondrially-mediated apoptosis and oncogenesis [Wang et al, 2009;Noutsopoulos et al, 2010]. If localization of the VL30 RNA is important for its function in apoptosis or in oncogenesis, modulation of mtRNA import in general, or specifically targeting import of VL30 retroelement could represent novel approaches to the treatment of developmental disorders and in cancer research.…”

Section: Qrt-pcr Analysis Of Mtrna By Digitonin Titrationmentioning

confidence: 99%

Mitochondrially‐Imported RNA in Drug Discovery

Cannon

Irwin

Pinkert

2015

Drug Development Research

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The import of nuclear transcribed RNAs into mitochondria is an emerging area that presents a tremendous opportunity to develop human metabolic therapeutics. However, our knowledge base is quite limited. Much remains to be discovered regarding specific RNA localization and mechanisms of import. To identify novel RNAs imported into mitochondria, all RNAs within the mitochondria were characterized using next generation sequencing technology. Several nuclear transcribed RNAs were found within mitochondrial RNA (mtRNA) samples, including nuclear ribosomal RNAs, gamma satellite RNA and VL30 retroelement RNA. The presence of these RNAs within mitochondria coupled with RNA sequencing data from other laboratories investigating mtRNA processing, lead us to hypothesize that nuclease treatment of mitoplasts is insufficient for removing contaminating cytoplasmic RNAs. In contrast to traditional methodology, mitochondrial import was evaluated by qRT-PCR after stepwise removal of the outer mitochondrial membrane and subsequent lysis of mitochondria. This allowed identification of RNAs lost from the mitochondria with the same kinetics as mitochondrial DNA-transcribed RNAs. This approach provided an improved evaluation of nuclear RNA enrichment within mitochondrial membranes to characterize nuclease protection and mitochondrial import and identify false-positive detection errors. qRT-PCR results confirmed the presence of VL30 retroelement RNA within mitochondria and question the hypothesis that the RNA component of RNase P is imported. These results illustrate a reliable approach for evaluating the presence of RNAs within mitochondria and open new avenues of investigation relating to mtRNA biology and in targeting mitochondrial based therapeutics.

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“…A flourish of works has documented the involvement of retrotransposons in embryogenesis, cell differentiation, pluripotency, cell cycle, DNA repair, aging, genomic imprinting, X-chromosome inactivation, behavior, metabolism and immune responses [42,91,[124][125][126][127][128][129][130][131][132][133][134][135][136][137] . However, besides their beneficial impact on host cell, the perturbation and/or loss of cellular control mechanisms may lead to the onset of genetic or multifactorial diseases [80,138,139] .…”

Section: Retrotransposons As Determinants Of Stress-activated Responsmentioning

confidence: 99%

“…Stressmediated retrotransposon activation may result in their induced mobilization or alteration of host gene expression. Depending on the strength of the stress stimulus, such activation may confer adaptation, if the cell profits the recovery of the homeostatic balance [12] , or lead to a vulnerability of the genome [130,141] . Hence, retrotransposons act as genetic pieces prone to bridge the gap between stress and cellular response.…”

Section: Retrotransposons As Determinants Of Stress-activated Responsmentioning

confidence: 99%

On the Concept Of Retrotransposons: Controlling Genome and Making Stress Memories

Noutsopoulos

2016

Journal of Biochemistry and Molecular Biology Research

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Retrotransposons constitute discrete genetic entities that have attained a large fraction of mammalian genomes during evolution. Their inhabitance as well as their functional impact on host genome has definitively revised the initial viewpoint of "junk DNA". Nowadays, it is widely accepted that retrotransposons may control genome through a variety of mechanisms, affecting different cellular processes. Here, I survey their impact on genome architecture and function with an emphasis on their interwoven relationship with stress.

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VL30 retrotransposition signals activation of a caspase-independent and p53-dependent death pathway associated with mitochondrial and lysosomal damage

Cited by 27 publications

References 50 publications

RRP22: a novel neural tumor suppressor for astrocytoma

RRP22: a novel neural tumor suppressor for astrocytoma

Mitochondrially‐Imported RNA in Drug Discovery

On the Concept Of Retrotransposons: Controlling Genome and Making Stress Memories

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