ENHANCED CELL-FREE TRANSLATION OF HUMAN-SKIN COLLAGENASE IN RECESSIVE DYSTROPHIC EPIDERMOLYSIS BULLOSA

[摘要] The regulatory mechanisms for collagenase synthesis in recessive dystrophic epidermolysis bullosa (RDEB) was studied using mRNA harvested from normal and RDEB skin fibroblasts to direct protein synthesis in a rabbit reticulocyte lysate translation system. Fibroblast mRNA encoded the synthesis of .apprx. 60,000 and .apprx. 55,000 dalton forms of procollagenase in cell-free translation. In contrast to biosynthesis by intact cells, there was preferential translation of the .apprx. 60,000 dalton species. For quantitative comparisons with mRNA from normal cells, mRNA was harvested from fibroblasts of 2 RDEB patients whose intact cells have been documented to have increased synthesis of collagenase. Although total translational activity was equal in normal and RDEB mRNA preparations, translatable collagenase mRNA was increased 3.5- to 10-fold, suggesting that the enhanced collagenase synthesis characteristic of RDEB is due to increased concentrations or preferential translation of collagenase mRNA.