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

• Published in: The Journal of biological chemistry 1999-04, Vol.274 (16), p.11060-11071
• Main Authors: Li, B L, Li, X L, Duan, Z J, Lee, O, Lin, S, Ma, Z M, Chang, C C, Yang, X Y, Park, J P, Mohandas, T K, Noll, W, Chan, L, Chang, T Y
• Format: Article
• Language: English
• Subjects: 5' Untranslated Regions; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 7; DNA; Exons; Humans; Introns; Promoter Regions, Genetic; Restriction Mapping; RNA, Messenger - genetics; Sterol O-Acyltransferase - genetics
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.274.16.11060

Acyl-CoA:cholesterol acyltransferase (ACAT) plays important roles in cellular 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 coding sequence (exons 2–15). The 4.3-kb mRNA contains an additional 5′-untranslated 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 exons 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 mapping shows that exons 1–16 and the P1 promoter sequences are located in chromosome 1, while exon X a and the P7 promoter sequence are located in chromosome 7. RNase protection assays demonstrate three different protected fragments, corresponding to the 4.3-kb mRNA and the two other mRNAs transcribed from 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.