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Comparing proteomics and RISC immunoprecipitations to identify targets of Epstein-Barr viral miRNAs [RISC-IP-seq]

ABSTRACT: Epstein-Barr virus is a gamma-herpes virus that is causally associated with several lymphomas and carcinomas. This virus encodes at least 25 pre-miRNAs, which are expressed in infected cells to yield more than 50 detected mature miRNAs. miRNAs are small, non-coding RNAs that inhibit gene expression by promoting the inhibition of translation or of degradation of mRNAs. Currently, the function of these viral miRNAs and the contribution they provide to EBV's life-cycle remain largely unknown, due to difficulties in identifying cellular and viral genes regulated by these miRNAs. We have compared and contrasted two methods to identify targets of viral miRNAs in order to identify the advantages and limitations of each method to aid in uncovering the functions of EBV's miRNAs.

ORGANISM(S): Homo sapiens

PROVIDER: GSE46514 | GEO | 2013/05/01

SECONDARY ACCESSION(S): PRJNA200712

REPOSITORIES: GEO

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Comparing proteomics and RISC immunoprecipitations to identify targets of Epstein-Barr viral miRNAs [RISC-IP-seq]

Project description:Epstein-Barr virus is a gamma-herpes virus that is causally associated with several lymphomas and carcinomas. This virus encodes at least 25 pre-miRNAs, which are expressed in infected cells to yield more than 50 detected mature miRNAs. miRNAs are small, non-coding RNAs that inhibit gene expression by promoting the inhibition of translation or of degradation of mRNAs. Currently, the function of these viral miRNAs and the contribution they provide to EBV's life-cycle remain largely unknown, due to difficulties in identifying cellular and viral genes regulated by these miRNAs. We have compared and contrasted two methods to identify targets of viral miRNAs in order to identify the advantages and limitations of each method to aid in uncovering the functions of EBV's miRNAs. Examination of RISC (RNA Induced Silencing Complexes) associated transcripts under 2 conditions in BJAB cells

2013-05-01 | E-GEOD-46514 | biostudies-arrayexpress

MaHo002: Epstein-Barr virus miRNA BART16 suppresses type I interferon signaling

Project description:The prototypic gammaherpesvirus Epstein-Barr virus (EBV) is carried by over 90% of the adult human population. Although infection often proceeds asymptomatically, the virus is causally involved in infectious mononucleosis and various malignancies. Like all herpesviruses, EBV establishes a lifelong latent infection in its human host. To successfully establish a persistent infection and spread to new hosts, EBV needs to avoid clearance by the host immune system. In addition to ~100 proteins, some of which perform immunomodulatory functions, EBV encodes over 40 mature miRNAs. Cellular miRNAs regulate diverse cellular processes, but the functions of the EBV miRNAs remain poorly understood. In this study, we identify EBV-encoded miR-BART16 as a novel viral immune evasion factor that interferes with host type I IFN responses. miR-BART16-5p downregulates the cellular histone acetyltransferase CBP (CREBB-binding protein) by directly targeting the CBP-encoding mRNA. CBP plays an important role in the type I IFN signaling pathway. Inhibiting endogenously expressed miR-BART16 in EBV-transformed B cells and gastric carcinoma cells results in increased CBP levels. Consistent with the important role of CBP in type I IFN signaling, miR-BART16 expression interferes with ISRE-promoter activity and production of interferon-stimulated genes in response to IFN-α treatment. These combined data show that EBV employs miRNAs to modify IFN-induced gene transcription. Given the importance of the host IFN system in the antiviral defence, obstructing this response may provide a way for EBV to favour viral replication and could play an etiological role in EBV-associated malignancies.

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Epstein-Barr virus maintains lymphomas via its miRNAs

Project description:EpsteinM-bM-^@M-^PBarr virus (EBV) has evolved exquisite controls over its host cells, human B lymphocytes, not only directing these cells during latency to proliferate and thereby expand the pool of infected cells, but also to survive and thereby persist for the lifetime of the infected individual. Although these activities ensure the virus is successful, they also make the virus oncogenic, particularly when infected people are immunosuppressed. Here we show, strikingly, that one set of EBVM-bM-^@M-^Ys miRNAs both sustain BL (BurkittM-bM-^@M-^Ys lymphoma) cells in the absence of other viral oncogenes and promote the transformation of primary B lymphocytes. BurkittM-bM-^@M-^Ys Lymphoma cells were engineered to lose EBV and found to die by apoptosis and could be rescued by constitutively expressing viral miRNAs in them. Two of these EBV miRNAs were found to target Caspase 3 to inhibit apoptosis at physiological concentrations. Examination of RISC associated transcripts under 4 conditions in Sav S1-1 cells

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Comparing proteomics and RISC immunoprecipitations to identify targets of Epstein-Barr viral miRNAs.

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