Differential expression of isomorphic HLA-DR beta genes is not a sole function of transcription.

Cells expressing HLA DR7 contain two functional DR beta genes, DRB1 and DRB4, whose mRNA is present at different levels. We examined whether the mRNA levels are due to differential transcriptional regulation or post-transcriptional regulation. As part of this analysis, a novel series of upstream elements was identified. Analysis of the proximal promoter activity, using a transient expression system, showed that the isomorphic promoter activities of B1 and B4 are about equal. RNase protection analysis of steady-state pre-mRNA and mRNA levels shows that the DR7 B1 pre-mRNA levels are 3 to 4 fold higher than B4 pre-mRNA levels. However, the B1 mRNA levels are increased seven fold relative to the B4 mRNA levels. The disproportionate increase of the mRNA levels relative to the corresponding pre-mRNA levels indicates that regulation also occurs at the post-transcriptional level.