Delineation of a core RNA element required for Kaposi's sarcoma-associated herpesvirus ORF57 binding and activity

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Abstract

The Kaposi's sarcoma-associated herpesvirus (KSHV) ORF57 protein is an essential multifunctional regulator of gene expression. ORF57 interaction with RNA is necessary for ORF57-mediated posttranscriptional functions, but little is known about the RNA elements that drive ORF57-RNA specificity. Here, we investigate the cis-acting factors on the KSHV PAN RNA that dictate ORF57 binding and activity. We show that ORF57 binds directly to the 5' end of PAN RNA in KSHV-infected cells. Furthermore, we employ in vitro and cell-based assays to define a 30-nucleotide (nt) core ORF57-responsive element (ORE) that is necessary and sufficient for ORF57 binding and activity. Mutational analysis of the core ORE further suggests that a 9-nt sequence is a specific binding site for ORF57. These studies provide insight into ORF57 specificity determinants and lay a foundation for future analyses of cellular and viral ORF57 targets.

Original languageEnglish (US)
Pages (from-to)107-116
Number of pages10
JournalVirology
Volume419
Issue number2
DOIs
StatePublished - Oct 25 2011

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Keywords

  • Gene expression
  • Kaposi's sarcoma-associated herpesvirus
  • ORF57/Mta
  • PAN RNA
  • Post-transcriptional gene regulation
  • RNA-binding

ASJC Scopus subject areas

  • Virology

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