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Thioredoxin post-transcriptional regulation by H19 provides a new function to mRNA-like non-coding RNA

Abstract

Classically, the functional product of coding genes is a protein whose synthesis is directed by an mRNA-template. However, in the last few years several genes yielding an mRNA-like non-coding RNA as a functional product have been identified. In most cases these transcripts are synthesized by the RNA polymerase II, capped, spliced and polyadenylated, like classical mRNA. These latter have non-conserved open reading frames and seem to be untranslated. Consequently, it has been proposed and admitted that these genes act at the RNA level, and are so-called ‘riboregulators’. H19 belongs to this class of gene and its role remains a matter of debate: for some authors it is an oncogene, for others a tumour suppressor. Here, we demonstrate, using a proteomic approach, that an H19 overexpression in human cancerous mammary epithelial cells stably transfected with genomic DNA containing the entire H19 gene is responsible for positively regulating at the post-transcriptional level the thioredoxin, a key protein of the cellular redox metabolism. Interestingly, this protein accumulates in many cancerous tissues, such as breast carcinomas in which we have also demonstrated an overexpression of the H19 gene.

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Acknowledgements

We thank C Montpellier for geneous gift of pRC/CMV-H19 vector. We thank J Kerr-Conte for her help with the English corrections. We thank L Brunet and G Courtand for their help in manuscript illustrations. We also thank J Antol and S Ruault for technical assistance. This work was supported by grants from the Association pour la Recherche sur le Cancer (ARC), the Groupement des Entreprises Françaises dans la Lutte contre le Cancer (GEFLUC) and the Ligue Nationale Contre le Cancer (Comité du Nord). S Lottin was financially supported by the ARC and the Fondation pour la Recherche Médicale (FRM). E Adriaenssens was recipient of an ARC fellowship.

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Correspondence to Jean-Jacques Curgy.

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Lottin, S., Vercoutter-Edouart, AS., Adriaenssens, E. et al. Thioredoxin post-transcriptional regulation by H19 provides a new function to mRNA-like non-coding RNA. Oncogene 21, 1625–1631 (2002). https://doi.org/10.1038/sj.onc.1205233

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Keywords

  • H19 gene
  • non-coding RNA
  • riboregulator
  • proteomic
  • thioredoxin
  • oncogene

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