MicroRNA-mediated transformation by the Kaposi's sarcomaassociated herpesvirus Kaposin locus

Eleonora Forte, Archana N. Raja, Priscilla Shamulailatpam, Mark Manzano, Matthew J. Schipma, John L. Casey, Eva Gottwein*

*Corresponding author for this work

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

The human oncogenic Kaposi's sarcoma-associated herpesvirus (KSHV) expresses a set of ~20 viral microRNAs (miRNAs). miR-K10a stands out among these miRNAs because its entire stem-loop precursor overlaps the coding sequence for the Kaposin (Kap) A/C proteins. The ectopic expression of KapA has been reported to lead to transformation of rodent fibroblasts. However, these experiments inadvertently also introduced miR-K10a, which raises the question whether the transforming activity of the locus could in fact be due to miR-K10a expression. To answer this question, we have uncoupled miR-K10a and KapA expression. Our experiments revealed that miR-K10a alone transformed cells with an efficiency similar to that when it was coexpressed with KapA. Maintenance of the transformed phenotype was conditional upon continued miR-K10a but not KapA protein expression, consistent with its dependence on miRNA-mediated changes in gene expression. Importantly, miR-K10a taps into an evolutionarily conserved network of miR-142-3p targets, several of which are expressed in 3T3 cells and are also known inhibitors of cellular transformation. In summary, our studies of miR-K10a serve as an example of an unsuspected function of an mRNA whose precursor is embedded within a coding transcript. In addition, our identification of conserved miR-K10a targets that limit transformation will point the way to a better understanding of the role of this miRNA in KSHV-associated tumors.

Original languageEnglish (US)
Pages (from-to)2333-2341
Number of pages9
JournalJournal of virology
Volume89
Issue number4
DOIs
StatePublished - 2015

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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