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MicroRNA-132 regulates antiviral innate immunity

Discussion in 'XMRV Research and Replication Studies' started by Rosemary, May 10, 2010.

  1. Rosemary

    Rosemary Senior Member

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    http://www.nature.com/ncb/journal/v12/n5/abs/ncb2054.html?lang=en

    Nature Cell Biology 12, 513 - 519 (2010)
    Published online: 25 April 2010 | doi:10.1038/ncb2054


    miR-132 regulates antiviral innate immunity through suppression of the p300 transcriptional co-activator
    Dimitrios Lagos1, Gabriel Pollara1, Stephen Henderson1, Fiona Gratrix1, Martin Fabani2, Richard S.B. Milne3, Frances Gotch4 & Chris Boshoff1

    MicroRNAs are small, non-coding RNAs that negatively regulate gene expression1. It has been proposed that microRNAs could function in the regulation of innate immunity2, 3, but this has not been demonstrated for viral infection. Here we test this hypothesis using the human pathogenic virus Kaposi's sarcoma-associated herpesvirus (KSHV) and one of its putative natural cellular targets, primary lymphatic endothelial cells4 (LECs). We show that an early antiviral microRNA response (6 h post-infection) includes expression of microRNAs that enhance viral gene expression. In particular, the CREB-induced miR-132 microRNA is highly upregulated after infection and has a negative effect on the expression of interferon-stimulated genes, facilitating viral replication. We show a similar function for miR-132 during infection of monocytes with herpes simplex virus-1 (HSV-1) and human cytomegalovirus (HCMV). miR-132 regulates innate antiviral immunity by inhibiting expression of the p300 transcriptional co-activator. p300 is downregulated early after KSHV infection, and inhibition of miR-132 induction restores p300 expression. Furthermore, p300 regulates miR-132 levels, revealing a dynamic equilibrium between miR-132 and p300. By targeting p300, rather than a transcription factor or signalling protein, miR-132 has a broad role in the regulation of antiviral immunity.
     
  2. Rosemary

    Rosemary Senior Member

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    http://www.miragentherapeutics.com/research/mirnas/

    What are microRNAs?
    microRNAs (miRNAs) are short (approximately 20-25 nucleotides long), single-stranded RNA molecules that regulate gene expression and play a vital role in influencing the pathways responsible for many illnesses, including cardiovascular and muscle disease. These RNAs are transcribed from genes; however, unlike messenger RNA (mRNA) they do not encode proteins.

    miRNAs function by preventing the translation of mRNAs into proteins and/or by triggering degradation of these mRNAs. Studies have shown that miRNA gene regulation is often not a decisive on and off switch but a subtle function that fine-tunes cellular phenotypes that becomes more pronounced during stress situations. miRNAs have been found in nearly every biological system examined to date. According to the Sanger Institute, over 850 miRNAs have been found in humans.

    miRNAs can be modulated with chemically synthesized oligonucleotides by either decreasing the levels (anti-miRs or inhibitors) or increasing the levels (pro-miRs or mimics) of expressed miRNAs. These modulators can then directly affect the protein expression of the specific miRNA’s targets. Typically, in laboratory settings, miRNA mimics are introduced as double stranded oligonucleotides and inhibitors are introduced as single strand oligonucleotides.


    MicroRNA-326 (miRNA-326)

    A study in patients and in mice suggests that inhibiting miRNA-326 could help treat MS. Further details on the research, next steps and licensing status are discussed in the article.

    http://www.nature.com/scibx/journal/v2/n41/full/scibx.2009.1527.html
     
  3. Rosemary

    Rosemary Senior Member

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    " Viruses may also perturb another class of effectors involved in RNAi called micro-RNAs (miRNAs), which are a class of cellular small RNAs generated by Dicer from hairpin structures. Cellular miRNA profiles are frequently modulated upon infection by viruses, and this may contribute in some cases to infectivity and pathogenesis [30]. Conversely, some viruses usurp the host miRNA machinery for processing miRNA-like structures encoded in the viral genome, potentially using these molecules for regulation of virus/host gene expression [31]."

    http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1000764
     

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