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A viral microRNA functions as an orthologue of cellular miR-155

Item Type:Article
Title:A viral microRNA functions as an orthologue of cellular miR-155
Creators Name:Gottwein, E. and Mukherjee, N. and Sachse, C. and Frenzel, C. and Majoros, W.H. and Chi, J.T.A. and Braich, R. and Manoharan, M. and Soutschek, J. and Ohler, U. and Cullen, B.R.
Abstract:All metazoan eukaryotes express microRNAs (miRNAs), roughly 22-nucleotide regulatory RNAs that can repress the expression of messenger RNAs bearing complementary sequences. Several DNA viruses also express miRNAs in infected cells, suggesting a role in viral replication and pathogenesis. Although specific viral miRNAs have been shown to autoregulate viral mRNAs or downregulate cellular mRNAs, the function of most viral miRNAs remains unknown. Here we report that the miR-K12-11 miRNA encoded by Kaposi's-sarcoma-associated herpes virus (KSHV) shows significant homology to cellular miR-155, including the entire miRNA 'seed' region. Using a range of assays, we show that expression of physiological levels of miR-K12-11 or miR-155 results in the downregulation of an extensive set of common mRNA targets, including genes with known roles in cell growth regulation. Our findings indicate that viral miR-K12-11 functions as an orthologue of cellular miR-155 and probably evolved to exploit a pre-existing gene regulatory pathway in B cells. Moreover, the known aetiological role of miR-155 in B-cell transformation suggests that miR-K12-11 may contribute to the induction of KSHV-positive B-cell tumours in infected patients.
Keywords:3' Untranslated Regions, B-Lymphocytes, Basic-Leucine Zipper Transcription Factors, Cell Line, Fanconi Anemia Complementation Group Proteins, Gene Expression Profiling, Gene Expression Regulation, Human Herpesvirus 8, MicroRNAs, Nucleic Acid Sequence Homology, Proto-Oncogene Proteins c-fos, Substrate Specificity, Viral Cell Transformation, Viral RNA
Publisher:Nature Publishing Group
Page Range:1096-1099
Date:13 December 2007
Official Publication:https://doi.org/10.1038/nature05992
PubMed:View item in PubMed

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