Academic Journal
Combined agonist-antagonist genome-wide functional screening identifies broadly active antiviral microRNAs
العنوان: | Combined agonist-antagonist genome-wide functional screening identifies broadly active antiviral microRNAs |
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المؤلفون: | Santhakumar, D., Forster, T., Laqtom, N. N., Fragkoudis, R, Dickinson, P., Abreu-Goodger, C., Manakov, S. A., Choudhury, N. R., Griffiths, S. J., Vermeulen, A., Enright, A. J., Dutia, B., Kohl, A., Ghazal, P., Buck, A. H. |
بيانات النشر: | National Academy of Sciences |
سنة النشر: | 2011 |
المجموعة: | University of Edinburgh: Edinburgh Research Archive (ERA) |
مصطلحات موضوعية: | RNAi, herpesvirus, RNA virus, RNA processing, phosphatidylinositol-3-kinase-Akt signalling |
الوصف: | Although the functional parameters of microRNAs ( miRNAs) have been explored in some depth, the roles of these molecules in viral infections remain elusive. Here we report a general method for global analysis of miRNA function that compares the significance of both overexpressing and inhibiting each mouse miRNA on the growth properties of different viruses. Our comparative analysis of representatives of all three herpesvirus subfamilies identified host miRNAs with broad anti- and proviral properties which extend to a single-stranded RNA virus. Specifically, we demonstrate the broad antiviral capacity of miR-199a-3p and illustrate that this individual host-encoded miRNA regulates multiple pathways required and/or activated by viruses, including PI3K/AKT and ERK/MAPK signaling, oxidative stress signaling, and prostaglandin synthesis. Global miRNA expression analysis further demonstrated that the miR-199a/miR-214 cluster is down-regulated in both murine and human cytomegalovirus infection and manifests similar antiviral properties in mouse and human cells. Overall, we report a general strategy for examining the contributions of individual host miRNAs in viral infection and provide evidence that these molecules confer broad inhibitory potential against multiple viruses. |
نوع الوثيقة: | article in journal/newspaper |
وصف الملف: | application/pdf |
اللغة: | English |
تدمد: | 0027-8424 1091-6490 |
Relation: | http://www.pnas.org/content/107/31/13830; http://hdl.handle.net/1842/4826 |
DOI: | 10.1073/pnas.1008861107 |
الاتاحة: | http://hdl.handle.net/1842/4826 http://www.pnas.org/content/107/31/13830 https://doi.org/10.1073/pnas.1008861107 |
رقم الانضمام: | edsbas.D2A44953 |
قاعدة البيانات: | BASE |
تدمد: | 00278424 10916490 |
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DOI: | 10.1073/pnas.1008861107 |