Identification of Virus-Encoded MicroRNAs

Pfeffer, Sébastien; Zavolan, Mihaela; Grässer, Friedrich A.; Chien, Minchen; Russo, James J.; Ju, Jingyue; John, Bino; Enright, Anton J.; Marks, Debora S.; Sander, Chris; Tuschl, Thomas

doi:10.1126/science.1096781

Cited by 1,440 publications

(1,294 citation statements)

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“…Thus, abnormal metaphases were more frequent in cells expressing latency I compared with EBVÀ cells and further increased in cells expressing latency III, suggesting that different viral products may be critical for the induction and/or amplification of the phenotype (Figure 2). It is noteworthy that only EBNA1, the untranslated EBERs RNAs, some poorly characterized transcripts derived from BamHI A region of the viral genome and some even less well-characterized micro-RNAs have been detected in BL cells expressing latency I (Dolcetti and Masucci, 2003;Pfeffer et al, 2004), suggesting that these viral products are sufficient for the effect either directly or through modulation of cellular genes.…”

Section: Discussionmentioning

confidence: 99%

Epstein–Barr virus promotes genomic instability in Burkitt's lymphoma

et al. 2007

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Epstein-Barr virus (EBV) has been implicated in the pathogenesis of human malignancies but the mechanisms of oncogenesis remain largely unknown. Genomic instability and chromosomal aberrations are hallmarks of malignant transformation. We report that EBV carriage promotes genomic instability in Burkitt's lymphoma (BL). Cytogenetic analysis of EBVÀ and EBV þ BL lines and their sublines derived by EBV conversion or spontaneous loss of the viral genome revealed a significant increase in dicentric chromosomes, chromosome fragments and chromatid gaps in EBV-carrying cells. Expression of EBV latency I was sufficient for this effect, whereas a stronger effect was observed in cells expressing latency III. Telomere analysis by fluorescent in situ hybridization revealed an overall increase of telomere size and prevalence of telomere fusion and double strand-break fusion in dicentric chromosomes from EBV þ cells. Phosphorylated H2AX, a reporter of DNA damage and ongoing repair, was increased in virus-carrying cells in the absence of exogenous stimuli, whereas efficient activation of DNA repair was observed in both EBV þ and EBVÀ cells following treatment with etoposide. These findings point to induction of telomere dysfunction and DNA damage as important mechanisms for EBV oncogenesis.

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Section: Discussionmentioning

confidence: 99%

Epstein–Barr virus promotes genomic instability in Burkitt's lymphoma

et al. 2007

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“…30 It was not recognized until recent years that EBV expresses two families of microRNA, BHRF1 and BamHI A rightward transcripts (BART), during the replication cycle. 31 One of these two families of EBV microRNA is derived from BART, which were originally found to be expressed abundantly in NPC cells. 32 EBV expresses limited viral proteins in NPC cells, but encodes 22 BART pre-microRNAs which can be further What's new?…”

mentioning

confidence: 99%

Circulating Epstein–Barr virus microRNAs miR‐BART7 and miR‐BART13 as biomarkers for nasopharyngeal carcinoma diagnosis and treatment

Zhang

Zong

Shen

et al. 2014

Intl Journal of Cancer

103

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More than 75% of nasopharyngeal carcinoma (NPC) patients have already developed local or regional spread at diagnosis, which hampers effective treatment and results in a poor prognosis. It is essential to characterize more sensitive and specific biomarkers for screening of high risk individuals and assessment of NPC treatment effectiveness. NPC is an Epstein-Barr virus (EBV) associated tumor in which only a few viral proteins but more than 20 BamHI A rightward transcripts (BART) microRNAs are detected, at abundant levels. We hypothesized that these BART microRNAs may be novel biomarkers for NPC. Systematic analysis of EBV BART microRNA expression profiles in EBV latently infected Mutu I and Mutu III cell lines, EBV-harboring NPC and noncancerous NP cells found that miR-BART3, miR-BART7 and miR-BART13 microRNAs are highly expressed and regularly secreted into the extracellular environment of NPC cells. These BART microRNAs were evaluated for used as potential NPC biomarkers. Analysis of plasma specimens obtained from NPC patients (n 5 89), and healthy (n 5 28) and non-NPC tumor patient controls (n 5 18) found levels of both miR-BART7 and miR-BART13, but not miR-BART3, to be distinctly presence among NPC patients, with elevated levels being particularly apparent among patients with advanced disease. Receiver operating characteristic curve analysis combining miR-BART7 and miR-BART13 levels produces a 90% predictive value for the presence of NPC. Analysis of 41 NPC patients before and after radiotherapy showed that miR-BART7 and miR-BART13, but not miR-BART3, were diminished after treatment. These results indicate that EBV microRNAs, miR-BART7 and miR-BART13, may constitute useful new serological biomarkers for diagnosis of NPC and prediction of treatment efficacy.

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“…On the other hand, evolutionarily ancient microRNAs are also known in plants: miR166 is conserved between flowering plants, ferns, mosses, and hornworts. In addition to land-plants and metazoan animals, microRNAs have also been found in viral genomes, including the Epstein-Barr virus (Herpesviridae) [328] and HIV (Retroviridae) [26,310].…”

Section: Micrornasmentioning

confidence: 99%

“…Examples include the recently discovered viral microRNAs [26,310,328], the well-known VA1 RNA of adenoviruses [272], which is capable of inhibiting RNAi in human cells [256], the pRNA component of the packaging motor in some bacteriophages [18,138]. One might suspect that at least some of the conserved RNA structure elements that were discovered in computations surveys of RNA virus genomes [165,402,439] are also non-coding RNAs rather than cis-acting elements.…”

Section: Other Classes Of Small Ncrnamentioning

confidence: 99%

Evolutionary patterns of non-coding RNAs

Bompfünewerer

Flamm

Fried

et al. 2005

Theory in Biosciences

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A plethora of new functions of non-coding RNAs have been discovered in past few years. In fact, RNA is emerging as the central player in cellular regulation, taking on active roles in multiple regulatory layers from transcription, RNA maturation, and Manuscript January 2005RNA modification to translational regulation. Nevertheless, very little is known about the evolution of this "Modern RNA World" and its components. In this contribution we attempt to provide at least a cursory overview of the diversity of non-coding RNAs and functional RNA motifs in non-translated regions of regular messenger RNAs (mRNAs) with an emphasis on evolutionary questions. This survey is complemented by an in-depth analysis of examples from different classes of RNAs focusing mostly on their evolution in the vertebrate lineage. We present a survey of Y RNA genes in vertebrates, studies of the molecular evolution of the U7 snRNA, the snoRNAs E1/U17, E2, and E3, the Y RNA family, the let-7 microRNA family, and the mRNA-like evf-1 gene. We furthermore discuss the statistical distribution of microRNAs in metazoans, which suggests an explosive increase in the microRNA repertoire in vertebrates. The analysis of the transcription of non-coding RNAs (ncRNAs) suggests that small RNAs in general are genetically mobile in the sense that their association with a hostgene (e.g. when transcribed from introns of a mRNA) can change on evolutionary time scales. The let-7 family demonstrates, that even the mode of transcription (as intron or as exon) can change among paralogous ncRNA.

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Identification of Virus-Encoded MicroRNAs

Cited by 1,440 publications

References 12 publications

Epstein–Barr virus promotes genomic instability in Burkitt's lymphoma

Epstein–Barr virus promotes genomic instability in Burkitt's lymphoma

Circulating Epstein–Barr virus microRNAs miR‐BART7 and miR‐BART13 as biomarkers for nasopharyngeal carcinoma diagnosis and treatment

Evolutionary patterns of non-coding RNAs

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