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Structure of the Carnitine Palmitoyltransferase‐1A Gene in Rats, Mice and Humans
Author(s) -
Cook George A.,
Park Edwards A.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1009.6
Subject(s) - exon , carnitine palmitoyltransferase i , biology , carnitine o palmitoyltransferase , gene , complementary dna , carnitine , gene expression , microbiology and biotechnology , messenger rna , beta oxidation , endocrinology , fatty acid , biochemistry
Carnitine Palmitoyltransferase‐1A (CPT1A) is expressed in all tissues of mammals except skeletal muscle and adipose tissue. CPT1A is the key regulatory enzyme of long‐chain fatty acid oxidation, and it is especially important in liver and kidney where it is important for controlling ketogenesis. When inhibited by its physiological inhibitor, malonyl‐CoA, CPT1A is also important for directing fatty acids into pathways of esterification resulting in increased secretion of lipoproteins. Since knowledge of the structure and control of the CPT1A gene will be important for understanding diabetes, altered thyroid states, and other aberrant energy states, we examined gene sequence data, genomic structure and mRNA expression data in rats, mice and human cell lines. We initially used RACE reactions to produce the full‐length rat cDNA and discovered that the initially published sequence for the rat cDNA did not include the most upstream exons. In experiments reported here, we used real‐time PCR to examine the structure of genes encoding CPT1A in these three species to see which exons were expressed in each species. The human CPT1A gene expresses 2 alternative exons (1a and 1b) upstream of the exon containing the start site for transcription. We found that the rat gene expresses a similar but larger exon (340 bp vs. 163 bp) that is approximately the same distance upstream (28 kbp) of the ATG. Furthermore, we found that rat gene expresses 3 additional intervening exons, all of which are different, both in size and location, from the human exon 1b. The mouse liver also expresses an initial exon in the same position as the human and rat gene, and it has 89% similarity with the rat exon 1a. The mouse also has sequences that are approx. 90% similar to the two additional rat exons, but they were not found to be expressed in mature mouse mRNA. In conclusion, the rat liver expresses at least 4 CPT1A mRNA species, whereas there are only 2 species expressed in humans. In mouse liver, 2 species of mRNA are expressed, but they are substantially different from the human mRNA species.