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

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Gottwein, E; Mukherjee, N; Sachse, C; Frenzel, C; Majoros, WH; Chi, J-TA; Braich, R; Manoharan, M; Soutschek, J; Ohler, U; Cullen, BR

Published Date

  • December 13, 2007

Published In

Volume / Issue

  • 450 / 7172

Start / End Page

  • 1096 - 1099

PubMed ID

  • 18075594

Electronic International Standard Serial Number (EISSN)

  • 1476-4687

Digital Object Identifier (DOI)

  • 10.1038/nature05992

Language

  • eng

Conference Location

  • England