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

作者：Snyder SR; Waring JF; Zhu SZ; Kaplan S; Schultz J; Ginder GD^*

来源：The Journal of Immunology, 2001, 166(6): 3966-3974.

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-AZ, 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-AZ mRNA, Formation of the 3' end was unaffected by IFN-gamma treatment. Sequences that mediate the majority of IFN-gamma induction of HLA-AZ 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.

• 出版日期2001-3-15