This Article Full Text Full Text (PDF) Other Versions of this Article: JVI.01313-07v1 81/24/13771    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dölken, L. Articles by Pfeffer, S. Search for Related Content PubMed PubMed Citation Articles by Dölken, L. Articles by Pfeffer, S.

 Previous Article  |  Next Article 

Journal of Virology, December 2007, p. 13771-13782, Vol. 81, No. 24
0022-538X/07/$08.00+0     doi:10.1128/JVI.01313-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Mouse Cytomegalovirus MicroRNAs Dominate the Cellular Small RNA Profile during Lytic Infection and Show Features of Posttranscriptional Regulation

Lars Dölken,¹ Jonathan Perot,² Valérie Cognat,² Abdelmalek Alioua,² Matthias John,^3, Jürgen Soutschek,^3, Zsolt Ruzsics,¹ Ulrich Koszinowski,¹ Olivier Voinnet,² and Sébastien Pfeffer^2*

Max von Pettenkofer-Institut für Virologie, Ludwig-Maximilians-Universität München, Pettenkoferstr. 9a, 80336 München, Germany,¹ IBMP-CNRS, 12, rue du Général Zimmer, 67084 Strasbourg Cedex, France,² Alnylam Europe AG, Fritz-Hornschuch-Str. 9, 95326 Kulmbach, Germany³

Received 15 June 2007/ Accepted 3 October 2007

MicroRNAs (miRNAs) are small, noncoding RNA molecules that regulate gene expression at the posttranscriptional level. Originally identified in a variety of organisms ranging from plants to mammals, miRNAs have recently been identified in several viruses. Viral miRNAs may play a role in modulating both viral and host gene expression. Here, we report on the identification and characterization of 18 viral miRNAs from mouse fibroblasts lytically infected with the murine cytomegalovirus (MCMV). The MCMV miRNAs are expressed at early times of infection and are scattered in small clusters throughout the genome with up to four distinct miRNAs processed from a single transcript. No significant homologies to human CMV-encoded miRNAs were found. Remarkably, as soon as 24 h after infection, MCMV miRNAs constituted about 35% of the total miRNA pool, and at 72 h postinfection, this proportion was increased to more than 60%. However, despite the abundance of viral miRNAs during the early phase of infection, the expression of some MCMV miRNAs appeared to be regulated. Hence, for three miRNAs we observed polyuridylation of their 3' end, coupled to subsequent degradation. Individual knockout mutants of two of the most abundant MCMV miRNAs, miR-m01-4 and miR-M44-1, or a double knockout mutant of miR-m21-1 and miR-M23-2, incurred no or only a very mild growth deficit in murine embryonic fibroblasts in vitro.

Published ahead of print on 17 October 2007.

Present address: Roche Kulmbach GmbH, Fritz-Hornschuch-Str. 9, D-95326 Kulmbach, Germany.

Present address: Regulus Therapeutics, 1896 Rutherford Road, Carlsbad, CA 92008-7208.

This article has been cited by other articles:

• Hussain, M., Taft, R. J., Asgari, S. (2008). An Insect Virus-Encoded MicroRNA Regulates Viral Replication. J. Virol. 82: 9164-9170 [Abstract] [Full Text]  
• Buck, A. H., Santoyo-Lopez, J., Robertson, K. A., Kumar, D. S., Reczko, M., Ghazal, P. (2007). Discrete Clusters of Virus-Encoded MicroRNAs Are Associated with Complementary Strands of the Genome and the 7.2-Kilobase Stable Intron in Murine Cytomegalovirus. J. Virol. 81: 13761-13770 [Abstract] [Full Text]