title: Mouse cytomegalovirus microRNAs dominate the cellular small RNA profile during lytic infection and show features of posttranscriptional regulation.
abstract: 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.
authors.affiliation: Max von Pettenkofer-Institut für Virologie, Ludwig-Maximilians-Universität München, Pettenkoferstr. 9a, 80336 München, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Dölken
authors.forename: Jonathan
authors.initials: J
authors.lastname: Perot
authors.forename: Valérie
authors.initials: V
authors.lastname: Cognat
authors.forename: Abdelmalek
authors.initials: A
authors.lastname: Alioua
authors.forename: Matthias
authors.initials: M
authors.lastname: John
authors.forename: Jürgen
authors.initials: J
authors.lastname: Soutschek
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Ruzsics
authors.forename: Ulrich
authors.initials: U
authors.lastname: Koszinowski
authors.forename: Olivier
authors.initials: O
authors.lastname: Voinnet
authors.forename: Sébastien
authors.initials: S
authors.lastname: Pfeffer
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D005260:Female; D005347:Fibroblasts / Q000821:virology; D015967:Gene Expression Regulation, Viral; D015723:Gene Library; D006566:Herpesviridae Infections / Q000821:virology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D018146:Muromegalovirus / Q000235:genetics / Q000472:pathogenicity*; D009154:Mutation; D041681:NIH 3T3 Cells; D012313:RNA / Q000235:genetics* / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D012367:RNA, Viral / Q000235:genetics* / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D012367:RNA, Viral; D012313:RNA