Blog
About

  • Record: found
  • Abstract: found
  • Article: not found

A 3'-transcribed region of the HLA-A2 gene mediates posttranscriptional stimulation by IFN-gamma.

Read this article at

ScienceOpenPubMed
Bookmark
      There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

      Abstract

      The expression of several MHC class I genes is up-regulated at the transcriptional level by IFN-gamma. Posttranscriptional mechanisms also have been implicated, but not well characterized. To investigate the mechanism of IFN-gamma stimulation of the human MHC class I gene HLA-A2, several human tumor cell lines were transfected with reporter gene constructs driven by the HLA-A2 promoter. We have previously shown that the extended 525-bp HLA-A2 promoter alone, which includes a 5' IFN-stimulated response element consensus sequence, is not sufficient for IFN-gamma response in either K562 or Jurkat cells. In the current study, stable transfection of a genomic HLA-A2 gene construct, containing both 5'- and 3'-flanking sequences, resulted in stimulation of the gene by IFN-gamma. Nuclear run-on assays revealed that, unlike other class I genes, IFN-gamma stimulation of HLA-A mRNA accumulation occurs almost entirely through posttranscriptional mechanisms. RNA stability assays showed that the effect is not mediated by alteration of the half-life of the HLA-A2 mRNA. Formation of the 3' end was unaffected by IFN-gamma treatment. Sequences that mediate the majority of IFN-gamma induction of HLA-A2 mRNA reside in a 127-bp 3'-transcribed region of the gene. This region contains the terminal splice site, the usage of which is not affected by IFN-gamma treatment. These results demonstrate a novel posttranscriptional mechanism of regulation of MHC class I genes by IFN-gamma.

      Related collections

      Author and article information

      Affiliations
      [1 ] Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA.
      Journal
      J. Immunol.
      Journal of immunology (Baltimore, Md. : 1950)
      0022-1767
      0022-1767
      Mar 15 2001
      : 166
      : 6
      11238642

      Comments

      Comment on this article