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

Eva Gottwein, Neelanjan Mukherjee, Christoph Sachse, Corina Frenzel, William H. Majoros, Jen Tsan A Chi, Ravi Braich, Muthiah Manoharan, Jürgen Soutschek, Uwe Ohler, Bryan R. Cullen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

473 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1096-1099
Number of pages4
JournalNature
Volume450
Issue number7172
DOIs
StatePublished - Dec 13 2007

ASJC Scopus subject areas

  • General

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