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Down-Regulation of a Host MicroRNA by a Herpesvirus saimiri Noncoding RNA

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Science  18 Jun 2010:
Vol. 328, Issue 5985, pp. 1563-1566
DOI: 10.1126/science.1187197

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Herpes Virus MiRNA Modulation

Viruses use a number of strategies to manipulate the cells of their host to ensure a successful infection. Herpesvirus saimiri (HVS) generates highly conserved small noncoding RNAs HSUR 1 and HSUR 2, which modulate expression of a number of proteins in infected primate T cells. Cazalla et al. (p. 1563; see the Perspective by Pasquinelli) observed complementarity between HSUR sequences and the seed regions of three different miRNAs—miR-142-3p, miR-27, and miR-16—and found that these HSURs could bind to the miRNAs. Furthermore, the level of mature miR-27 was modulated by binding to HSUR 1, which targeted the miRNA for degradation.

Abstract

T cells transformed by Herpesvirus saimiri express seven viral U-rich noncoding RNAs of unknown function called HSURs. We noted that conserved sequences in HSURs 1 and 2 constitute potential binding sites for three host-cell microRNAs (miRNAs). Coimmunoprecipitation experiments confirmed that HSURs 1 and 2 interact with the predicted miRNAs in virally transformed T cells. The abundance of one of these miRNAs, miR-27, is dramatically lowered in transformed cells, with consequent effects on the expression of miR-27 target genes. Transient knockdown and ectopic expression of HSUR 1 demonstrate that it directs degradation of mature miR-27 in a sequence-specific and binding-dependent manner. This viral strategy illustrates use of a ncRNA to manipulate host-cell gene expression via the miRNA pathway.

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