Human acyl-CoA : cholesterol acyltransferase-1 (ACAT-1) gene organization and evidence that the 4.3-kilobase ACAT-1 mRNA is produced from two different chromosomes

Acyl-CoA:cholesterol acyltransferase (ACAT) plays important roles in cellul ar cholesterol homeostasis. Four human ACAT-1 mRNAs (7.0, 4.3, 3.6, and 2.8 kilobases (kb)) share the same short 5'-untranslated region (exon 1) and c oding sequence (exons 2-15). The 4.3-kb mRNA contains an additional 5'-untr anslated region (1289 nucleotides in length; exons X-a and X-b) immediately upstream from the exon 1 sequence. One ACAT-1 genomic DNA insert covers ex ons 1-16 and a promoter (the P1 promoter). A separate insert covers exon X- a (1277 base pairs) and a different promoter (the P7 promoter). Gene mappin g shows that exons 1-16 and the P1 promoter sequences are located in chromo some 1, while exon X-a and the P7 promoter sequence are located in chromoso me 7. RNase protection assays demonstrate three different protected fragmen ts, corresponding to the 4.3 kb mRNA and the two other mRNAs transcribed fr om the two promoters. These results are consistent with the interpretation that the 4.3-kb mRNA is produced from two different chromosomes, by a novel RNA recombination mechanism involving trans-splicing of two discontinuous precursor RNAs.