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

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MicroRNA-based Regulation of Picornavirus Tropism
09:05

MicroRNA-based Regulation of Picornavirus Tropism

Published on: February 6, 2017

Grégoire Stik1, Sylvie Laurent, Damien Coupeau

  • 1Transcription, Lymphome Viro-Induit, University François Rabelais, UFR Sciences et Techniques, Parc de Grandmont, F-37200 Tours, France.

RNA (New York, N.Y.)
|October 1, 2010
PubMed

Insights

The tumor suppressor protein p53 directly targets viral microRNAs from gallid herpesvirus 2. This interaction is crucial, as virulent viral strains possess p53-responsive elements, unlike avirulent strains.

Area of Science:

  • Molecular Biology
  • Virology
  • Oncology

Background:

  • The tumor suppressor protein p53 is vital for cellular responses to cancer.
  • p53 regulates cell cycle progression and transactivates proapoptotic microRNA-34 family members.
  • MicroRNA-34 family members are frequently underexpressed in various cancers.

Purpose of the Study:

  • To investigate the interaction between the tumor suppressor protein p53 and microRNAs encoded by gallid herpesvirus 2 (GaHV-2).
  • To characterize the promoter region of the GaHV-2 latency-associated microRNA cluster and its regulation by p53.

Main Methods:

  • Reporter assays were performed in three avian cell lines to assess transcriptional activity.
  • Analysis of transcription start sites for the viral pri-miRNA transcript.
  • Site-directed mutagenesis was used to investigate the role of p53-responsive elements (RE) in promoter activity.

Main Results:

  • A sequence upstream of the GaHV-2 microRNA cluster demonstrated robust transcriptional activity.
  • The promoter lacks consensus core elements but contains tandem repeats with p53-responsive elements.
  • Mutagenesis of the p53 RE abolished transcriptional activity, while p53 induction enhanced mature microRNA expression.

Conclusions:

  • The latency-associated microRNA cluster of GaHV-2 is a direct transcriptional target of p53.
  • The presence of p53-regulated viral microRNA promoters correlates with GaHV-2 virulence.
  • This finding highlights a significant link between a host tumor suppressor and viral oncogene expression, with implications for cancer biology.

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