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.