A p53-dependent promoter associated with polymorphic tandem repeats controls the expression of a viral transcript encoding clustered microRNAs

Grégoire Stik, Sylvie Laurent, Damien Coupeau, Baptiste Coutaud, Ginette Dambrine, Denis Rasschaert, Benoît Muylkens

Research output: Contribution to journalArticle

Abstract

The tumor suppressor protein p53 plays a role in cellular responses to cancer-initiating events by regulating progress through the cell cycle. Several recent studies have shown that p53 transactivates expression of the members of the proapoptotic microRNA-34 family, which are underexpressed in several cancers. We demonstrate here that the latency-associated cluster of microRNAs (miRNA) encoded by an oncogenic herpesvirus, gallid herpesvirus 2 (GaHV-2), is a direct target of p53. Robust transcriptional activity was induced in three avian cell lines by a sequence mapping 600 base pairs (bp) upstream of the cluster of miRNAs. We found transcription start sites for the pri-miRNA transcript at the 3′ end of this transcription-inducing sequence. The promoter has no consensus core promoter element, but is organized into a variable number of tandem repeats of 60-bp harboring p53-responsive elements (RE). The minimal functional construct consists of two tandem repeats. Mutagenesis to change the sequence of the p53 RE abolished transcriptional activity, whereas p53 induction enhanced mature miRNA expression. The identification of a viral miRNA promoter regulated by p53 is biologically significant, because all avirulent GaHV-2 strains described to date lack the corresponding regulatory sequence, whereas all virulent, very virulent, and hypervirulent strains possess at least two tandem repeats harboring the p53 RE. Copyright © 2010 RNA Society.

Original languageEnglish
Pages (from-to)2263-2276
Number of pages14
JournalRNA
Volume16
Issue number11
DOIs
Publication statusPublished - Nov 2010

Fingerprint

Tandem Repeat Sequences
MicroRNAs
Gallid Herpesvirus 2
Base Pairing
Tumor Suppressor Protein p53
Minisatellite Repeats
Herpesviridae
Transcription Initiation Site
Mutagenesis
Neoplasms
Cell Cycle
Cell Line

Keywords

  • Herpesvirus
  • MicroRNA
  • p53
  • Promoter

Cite this

Stik, Grégoire ; Laurent, Sylvie ; Coupeau, Damien ; Coutaud, Baptiste ; Dambrine, Ginette ; Rasschaert, Denis ; Muylkens, Benoît. / A p53-dependent promoter associated with polymorphic tandem repeats controls the expression of a viral transcript encoding clustered microRNAs. In: RNA. 2010 ; Vol. 16, No. 11. pp. 2263-2276.
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A p53-dependent promoter associated with polymorphic tandem repeats controls the expression of a viral transcript encoding clustered microRNAs. / Stik, Grégoire; Laurent, Sylvie; Coupeau, Damien; Coutaud, Baptiste; Dambrine, Ginette; Rasschaert, Denis; Muylkens, Benoît.

In: RNA, Vol. 16, No. 11, 11.2010, p. 2263-2276.

Research output: Contribution to journalArticle

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