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J Biol Chem, Vol. 274, Issue 16, 11060-11071, April 16, 1999

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

Bo-Liang Li^§, Xia-Lu Li^§, Zhi-Jun Duan^§, Oneil Lee, Song Lin, Zhang-Mei Ma, Catherine C. Y. Chang, Xin-Ying Yang^§, Jonathan P. Park^**, T. K. Mohandas^**, Walter Noll^**, Lawrence Chan, and Ta-Yuan Chang

From the  Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, ^§ Shanghai Institute of Biochemistry, Shanghai, China,  Departments of Cell Biology and Medicine, Baylor College of Medicine, Houston, Texas 77030, and the ^** Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire 03756

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.

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