SV40 Large T Antigen Up-regulates the Retrotransposition Frequency of Viral-like 30 Elements

Noutsopoulos, Dimitrios; Vartholomatos, George; Kolaitis, Nicolaos; Tzavaras, Theodore

doi:10.1016/j.jmb.2006.06.030

Cited by 20 publications

(69 citation statements)

References 54 publications

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“…The results reported here and in other studies (5)(6)(7)12) suggest that tumorigenic pathways are initiated and driven by increased expression of PSF-binding RNAs, which reverse repression of proto-oncogenes by PSF. The regulation of tumorigenesis by PSF and PSF-binding RNAs identifies 2 previously undescribed markers for tumor cells: a reduced level of proto-oncogene promoters bound to PSF and an elevated level of PSF-binding RNAs.…”

Section: Discussionsupporting

confidence: 75%

“…PSF and VL30-1 RNA appear to have a primary role in tumorigenesis, because a decrease of PSF expression or increase of VL30-1 RNA expression transforms NIH/3T3 cells, whereas an increase of PSF expression or decrease of VL30-1 RNA expression suppresses tumorigenesis of B16F10 cells. Although VL30-1 RNA can integrate into the cell genome (3,12), the tumorpromoter function of VL30-1 RNA involves a trans effect rather than a cis effect on gene transcription. A similar regulatory mechanism functions in human cells with human PSF-binding RNAs replacing VL30-1 RNA (13), which is not encoded in the human genome.…”

Section: Discussionmentioning

confidence: 99%

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Regulation of proto-oncogene transcription, cell proliferation, and tumorigenesis in mice by PSF protein and a VL30 noncoding RNA

Wang

Cui

Zhang

et al. 2009

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

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cancer therapy ͉ Rab23 ͉ regulatory RNA ͉ tumor suppression P receding studies have described a reversible mechanism controlling gene transcription that involves PSF protein (1) and VL30-1 RNA, a member of the VL30 family of mouse retroelement noncoding RNAs (2, 3). PSF contains a DNAbinding domain (DBD) that binds and represses transcription of genes that have a PSF-binding site (4-6) and 2 RNA-binding domains (RBDs) that bind VL30-1 RNA, forming a PSF-RNA complex that dissociates from a gene and activates transcription (5-7). Increasing expression of PSF in a human tumor cell suppressed tumorigenesis (6), and ectopic expression of VL30-1 RNA in a human tumor cell promoted metastasis (3). VL30 RNAs are expressed in virtually all tissues of adult mice (8) and are associated with Ras-mediated transformation of mouse fibroblast cells (9). Here, we extend our studies of the function of PSF and VL30-1 RNA to the regulation of proto-oncogene transcription, cell proliferation, and tumorigenesis in mice. The results indicate that PSF is a major tumor-suppressor protein and VL30-1 RNA is a major tumor-promoter RNA in mice. ResultsExpression of PSF and VL30 -1 RNA in NIH/3T3 and B16F10 Cell Lines.NIH/3T3 and B16F10 cells were transfected with a transgene encoding PSF (NIH/3T3-PSF1 and B16F10-PSF1 lines) or VL30-1 RNA (NIH/3T3-VL301 line) or with a plasmid encoding a shRNA that causes degradation of PSF mRNA (NIH/ 3T3-PSF2 line) or VL30 -1 RNA (NIH/3T3-VL302 and B16F10-VL302 lines). The control lines were transfected with an empty plasmid pcDNA3.1(ϩ) (NIH/3T3-pcDNA3.1 and B16F10-pcDNA3.1 cell lines) or a plasmid encoding shLuciferase (NIH/3T3-shLuc and B16F10-shLuc lines). The NIH/ 3T3 and B16F10 cell lines were assayed for expression of PSF mRNA and VL30-1 RNA ( Fig. 1 and Table 1) and PSF protein (Fig. 1).Binding of PSF to the Regulatory DNAs of Mouse Genes. Chromatin fragments from NIH/3T3 cells were coimmunoprecipitated with anti-PSF antibody, and the DNAs in the fragments were tested for hybridization to a mouse gene-promoter chip (NimbleGen; Roche) that contains 385,000 regulatory DNAs from the mouse genome. A total of 57 DNA fragments were identified by chip assay, of which 12 mapped to characterized mouse coding genes [supporting information (SI) Tables S1 and S2]. The 12 DNAs bound to PSF in NIH/3T3 and B16F10 cells, as shown by a ChIP assay (Fig. 2); the P450scc gene had been identified as a PSF-binding gene in earlier studies (4, 6). We chose the Rab23 gene, a member the RAS gene family (10,11), to analyze the role of PSF and VL30-1 RNA in the regulation of proto-oncogene transcription in mice. (Table 1). Binding of Rab23 DNA to PSF is higher in NIH/3T3-PSF1 and B16F10-PSF1 cells and lower in NIH/3T3-PSF2 cells than in NIH/3T3 or B16F10 control cells (Fig. 3A). (ii) Transcription of Rab23 was analyzed in the same cell lines by RT-PCR. Transcription is lower in NIH/3T3-PSF1 and B16F10-PSF1 cells and higher in NIH/3T3-PSF2 cells than in NIH/3T3 or B16F10 control cells (Fig. 3B). The results indicate that PSF bin...

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Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Regulation of proto-oncogene transcription, cell proliferation, and tumorigenesis in mice by PSF protein and a VL30 noncoding RNA

Wang

Cui

Zhang

et al. 2009

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

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“…Such retrotransposon-induced rearrangements can be passive, due to their repetitive nature as well as their high sequence homology, or active as a direct result of retrotransposition events [56][57][58][59][60][61][62][63][64][65][66][67] . Intriguingly, retrotransposition constitutes an important agent for generation of genetic variation [64][65][66][67][68][69][70][71][72][73][74][75][76][77][78][79][80][81] being responsible for 20% of the genome structural variation in humans [81] . Overall, retrotransposon-induced recombination seems to have a fundamental role in creation of genomic stability, diversity and plasticity.…”

Section: R E T R O T R a N S P O S O N S : A W E B O F Sophisticated mentioning

confidence: 99%

“…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] . So far, it is known that retrotransposon activity, concerning their transcription and retrotransposition, is induced during cellular processes among them cell proliferation and differentiation, as well as by numerous stress factors such as heavy metals, oxidative stress, UV irradiation, viral infection, and drugs [1,12,74,91,128,[140][141][142][143][144] . Nevertheless, our knowledge concerning the biology of TEs is still rudimentary.…”

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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“…Recently, it was reported that L1 retrotransposition induced apoptosis in human cancer cells [20,21]. Regarding mouse LTR retrotransposons, we reported that high induction of VL30 retrotransposition resulted in massive cell death or cytotoxic effects in NIH3T3 cells following either expression of SV40 large T-antigen (LT) [22] or vanadium-generated oxidative stress [23], respectively. Although these data demonstrated the effect of retrotransposition on PCD, the underlying mechanism remains to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2010

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SV40 Large T Antigen Up-regulates the Retrotransposition Frequency of Viral-like 30 Elements

Cited by 20 publications

References 54 publications

Regulation of proto-oncogene transcription, cell proliferation, and tumorigenesis in mice by PSF protein and a VL30 noncoding RNA

Regulation of proto-oncogene transcription, cell proliferation, and tumorigenesis in mice by PSF protein and a VL30 noncoding RNA

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

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

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