Dataset Information

Genomic non-redundancy of the mir-183/96/182 cluster and its requirement for hair cell maintenance.

ABSTRACT: microRNAs are important regulators of gene expression. In the retina, the mir-183/96/182 cluster is of particular interest due to its robust expression and studies in which loss of the cluster caused photoreceptor degeneration. However, it is unclear which of the three miRNAs in the cluster are ultimately required in photoreceptors, whether each may have independent, contributory roles, or whether a single miRNA from the cluster compensates for the loss of another. These are important questions that will not only help us to understand the role of these particular miRNAs in the retina, but will deepen our understanding of how clustered microRNAs evolve and operate. To that end, we have developed a complete panel of single, double, and triple mir-183/96/182 mutant zebrafish. While the retinas of all mutant animals were normal, the triple mutants exhibited acute hair cell degeneration which corresponded with impaired swimming and death at a young age. By measuring the penetrance of this phenotype in each mutant line, we determine which of the three miRNAs in the cluster are necessary and/or sufficient to ensure normal hair cell development and function.

SUBMITTER: Fogerty J

PROVIDER: S-EPMC6635406 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Genomic non-redundancy of the mir-183/96/182 cluster and its requirement for hair cell maintenance.

Fogerty Joseph J Stepanyan Ruben R Cianciolo Lauren T LT Tooke Benjamin P BP Perkins Brian D BD

Scientific reports 20190716 1

microRNAs are important regulators of gene expression. In the retina, the mir-183/96/182 cluster is of particular interest due to its robust expression and studies in which loss of the cluster caused photoreceptor degeneration. However, it is unclear which of the three miRNAs in the cluster are ultimately required in photoreceptors, whether each may have independent, contributory roles, or whether a single miRNA from the cluster compensates for the loss of another. These are important questions ...[more]

PMID: 31311951

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Project description:Epstein-Barr virus (EBV) is an oncogenic human herpesvirus involved in the pathogenesis of Burkitt's lymphoma (BL) and various other lymphoproliferative disorders. In BL, EBV protein expression is restricted to EBV nuclear antigen 1 (EBNA1), but small noncoding RNAs such as EBV-encoded small RNAs (EBERs) and microRNAs (miRNAs) can also be detected. miRNAs play major roles in crucial processes such as proliferation, differentiation, and cell death. It has recently become clear that alterations in the expression profile of miRNAs contribute to the pathogenesis of a number of malignancies. During latent infection, EBV expresses 25 viral pre-miRNAs and modulates the expression of specific cellular miRNAs, such as miR-155 and miR-146, which potentially play a role in oncogenesis. Here, we established the small-RNA expression profiles of three BL cell lines. Using large-scale sequencing coupled to Northern blotting and real-time reverse transcription-PCR (RT-PCR) analysis validation, we demonstrated the differential expression of some cellular and viral miRNAs. High-level expression of the miR-183-96-182 cluster and EBV miR-BamHI A rightward transcript (miR-BART) cluster was significantly associated with EBV type I latency. This expression was not affected by viral reactivation since transforming growth factor ?1 (TGF-?1) stimulation did not significantly change the miRNA profiles. However, using several approaches, including de novo infection with a mutant virus, we present evidence that the expression of latent membrane protein 1 (LMP-1) triggered downregulation of the expression of the miR-183-96-182 cluster. We further show that this effect involves the Akt signaling pathway.In addition to expressing their own miRNAs, herpesviruses also impact the expression levels of cellular miRNAs. This regulation can be either positive or negative and usually results in the perturbation of pathways to create a cellular environment that is more "virus-friendly." For example, EBV induces the expression of miR-155, a well-characterized oncomiR, which leads to increased cell proliferation and decreased cell death. Here, we show that EBV-encoded LMP-1 is also involved in the downregulation of a cluster of three miRNAs, miR-183, -96, and -182, which are known to be also repressed in several cancers. We therefore identify yet another potential player in EBV-induced oncogenesis.

Dataset Information

Genomic non-redundancy of the mir-183/96/182 cluster and its requirement for hair cell maintenance.

Publications

Genomic non-redundancy of the mir-183/96/182 cluster and its requirement for hair cell maintenance.

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