Post-transcriptional regulation of miR-27 in murine cytomegalovirus infection

In mammals, microRNAs (miRNAs) can play diverse roles in viral infection through their capacity to regulate both host and viral genes. Recent reports have demonstrated that specific miRNAs change in expression level upon infection and can impact viral production and infectivity. It is clear that miR...

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Published in:	RNA (Cambridge) Vol. 16; no. 2; pp. 307 - 315
Main Authors:	Buck, Amy H, Perot, Jonathan, Chisholm, Michael A, Kumar, Diwakar S, Tuddenham, Lee, Cognat, Valérie, Marcinowski, Lisa, Dölken, Lars, Pfeffer, Sébastien
Format:	Journal Article
Language:	English
Published:	United States Cold Spring Harbor Laboratory Press 01-02-2010
Subjects:	Animals Antiviral Agents - metabolism Base Sequence Biochemistry, Molecular Biology Cell Line Cellular Biology Cytomegalovirus Infections - genetics Cytomegalovirus Infections - metabolism DNA Primers - genetics Down-Regulation Life Sciences Mice MicroRNAs - genetics MicroRNAs - metabolism Molecular biology Muromegalovirus - pathogenicity Muromegalovirus - physiology NIH 3T3 Cells RNA Processing, Post-Transcriptional microRNA RNA silencing mouse cytomegalovirus regulation RNA processing small RNA profiling : herpesvirus
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Summary:	In mammals, microRNAs (miRNAs) can play diverse roles in viral infection through their capacity to regulate both host and viral genes. Recent reports have demonstrated that specific miRNAs change in expression level upon infection and can impact viral production and infectivity. It is clear that miRNAs are an integral component of viral-host interactions, and it is likely that both host and virus contain mechanisms to regulate miRNA expression and/or activity. To date, little is known about the mechanisms by which miRNAs are regulated in viral infection. Here we report the rapid down-regulation of miR-27a in multiple mouse cell lines as well as primary macrophages upon infection with the murine cytomegalovirus. Down-regulation of miR-27a occurs independently from two other miRNAs, miR-23a and miR-24, located within the same genomic cluster, and analysis of pri-miRNA levels suggest that regulation occurs post-transcriptionally. miR-27b, a close homolog of miR-27a (20/21 nucleotide identity), also decreases upon infection, and we demonstrate that both miR-27a and miR-27b exert an antiviral function upon over-expression. Drug sensitivity experiments suggest that virus entry is not sufficient to induce the down-regulation of miR-27 and that the mechanism requires synthesis of RNA. Altogether, our findings indicate that miR-27a and miR-27b have antiviral activity against MCMV, and that either the virus or the host encodes molecule(s) for regulating miR-27 accumulation, most likely by inducing the rapid decay of the mature species.
Bibliography:	PMCID: PMC2811660 Reprint requests to: Amy H. Buck, Centre for Immunity, Infection, and Evolution, Ashworth Laboratories, University of Edinburgh, West Mains Road, Edinburgh EH93JT, United Kingdom; e-mail: a.buck@ed.ac.uk; fax: 44-131-650-6564, or Sébastien Pfeffer, Architecture et Réactivité de l'ARN, Institut de Biologie Moléculaire et Cellulaire du Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg, 15 rue René Descartes, 67084 Strasbourg, France; e-mail: spfeffer@unistra.fr; fax: 33-388-602-218.
ISSN:	1355-8382 1469-9001
DOI:	10.1261/rna.1819210