Platelet-derived growth factor A chain: gene structure, chromosomal location, and basis for alternative mRNA splicing

Abstract

Genomic clones encoding the A chain of platelet-derived growth factor (PDGF) have been isolated. The gene contains seven exons spanning about 24 kilobases of DNA. The positions of intervening sequences closely match those of the related B-chain (c-sis) gene on chromosome 22. In situ hybridization was used to localize the PDGF A-chain gene to the distal portion of the short arm of chromosome 7 (7p21-p22). Within the (G + C)-rich 5' region, a single transcriptional start site was identified approximately equal to 36 base pairs downstream of a TATAA consensus promoter element. The three size classes of A-chain mRNA probably arise by selection of alternative poly(A) sites in exon 7, but only a single consensus AATAAA signal was identified in this region. Two functionally different A-chain precursors, which differ by the presence or absence of a basic C terminus, are generated as a result of alternative mRNA splicing events, which include or exclude exon 6. This and other structural features of the A-chain gene suggest that PDGF expression may be modulated at transcriptional and post-transcriptional levels.