Systematic analysis of viral and cellular microRNA targets in cells latently infected with human γ-herpesviruses by RISC immunoprecipitation assay

Lars Dölken, Georg Malterer, Florian Erhard, Sheila Kothe, Caroline C. Friedel, Guillaume Suffert, Lisa Marcinowski, Natalie Motsch, Stephanie Barth, Michaela Beitzinger, Diana Lieber, Susanne M. Bailer, Reinhard Hoffmann, Zsolt Ruzsics, Elisabeth Kremmer, Sébastien Pfeffer, Ralf Zimmer, Ulrich H. Koszinowski, Friedrich Grässer, Gunter MeisterJurgen Haas*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

189 Scopus citations

Abstract

The mRNA targets of microRNAs (miRNAs) can be identified by immunoprecipitation of Argonaute (Ago) protein-containing RNA-induced silencing complexes (RISCs) followed by microarray analysis (RIP-Chip). Here we used Ago2-based RIP-Chip to identify transcripts targeted by Kaposi's sarcomaassociated herpesvirus (KSHV) miRNAs (n = 114), Epstein-Barr virus (EBV) miRNAs (n = 44), and cellular miRNAs (n = 2337) in six latently infected or stably transduced human B cell lines. Of the six KSHV miRNA targets chosen for validation, four showed regulation via their 3'UTR, while two showed regulation via binding sites within coding sequences. Two genes governing cellular transport processes (TOMM22 and IP07) were confirmed to be targeted by EBV miRNAs. A significant number of viral miRNA targets were upregulated in infected cells, suggesting that viral miRNAs preferentially target cellular genes induced upon infection. Transcript half-life both of cellular and viral miRNA targets negatively correlated with recruitment to RISC complexes, indicating that RIP-Chip offers a quantitative estimate of miRNA function.

Original languageEnglish
Pages (from-to)324-334
Number of pages11
JournalCell Host and Microbe
Volume7
Issue number4
DOIs
StatePublished - 22 Apr 2010
Externally publishedYes

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