DIFFERENTIAL EXPRESSION OF EXONS 1A AND 1C IN MESSENGER-RNAS FOR STEROL REGULATORY ELEMENT-BINDING PROTEIN-1 IN HUMAN AND MOUSE ORGANS AND CULTURED-CELLS

The 5' end of the mRNA-encoding sterol regulatory element binding prot ein-1 (SREBP-1) exists in two forms, designated 1a and 1c. The diverge nce results from the use of two transcription start sites that produce two separate 5' exons, each of which is spliced to a common exon 2. H ere we show that the ratio of SREBP-1c to 1a transcripts varies marked ly among organs of the adult mouse. At one extreme is the liver, in wh ich the 1c transcript predominates by a 9:1 ratio. High 1c:1a ratios a re also found in mouse adrenal gland and adipose tissue and in human l iver and adrenal gland. At the other extreme is the spleen, which show s a reversed 1c:1a ratio (1:10). In five different lines of cultured c ells, including the HepG2 line derived from human hepatocytes, the 1a transcript predominated (1c:1a ratio < 1:2). In mouse 3T3-L1 preadipoc ytes, the 1a transcript was present, but the 1c transcript was not det ectable. When these cells were differentiated into adipocytes by hormo ne treatment in culture, the amount of 1a transcript rose markedly (8. 2-fold), and the 1c transcript remained virtually undetectable. We con clude that the SREBP-1a and 1c transcripts are controlled independentl y by regulatory regions that respond differentially to organ-specific and metabolic factors.