Structure of the rat gene encoding cholesterol 7.alpha.-hydroxylase

Abstract

Cholesterol 7.alpha.-hydroxylase (7.alpha.-hydroxylase) is a microsomal cytochrome P-450 that catalyzes the first and rate-limiting step in bile acid biosynthesis, the major catabolic pathway in cholesterol homeostasis. The gene encoding the rat 7.alpha.-hydroxylase has been isolated and characterized. Southern blotting experiments demonstrated that the gene is present in a single copy in the rat genome. DNA sequence analysis showed that the 7.alpha.-hydroxylase gene is unique among the characterized cytochrome P-450s in that it contains only six exons. Nuclease S1 and primer-extension mapping experiments positioned the 5''-ends of the 7.alpha.-hydroxylase mRNA approximately 20-25 nucleotides downstream of a consensus TATAAA sequence. RNA blotting experiments demonstrated the presence of multiple 7.alpha.-hydroxylase mRNAs that differ in the lengths of their 3''-untranslated regions.