Differential expression of exons 1a and 1c in mRNAs for sterol regulatory element binding protein-1 in human and mouse organs and cultured cells
Differential expression of exons 1a and 1c in mRNAs for sterol regulatory element binding protein-1 in human and mouse organs and cultured cells
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DOI：
10.1172/jci119247
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发表时间：
1997-03-01
影响因子：
15.9
通讯作者：
Brown, MS
中科院分区：
文献类型：
--
作者：
Shimomura, I;Shimano, H;Brown, MS
编码固醇调节元件结合蛋白-1(SREBP-1)的5‘端以两种形式存在，分别命名为1a和1c。这种差异是由于使用了两个转录起始点，它们产生了两个单独的5‘外显子，每个外显子都剪接到一个共同的外显子2。在这里，我们表明SREBP-1c和1a转录本的比例在成年小鼠的器官中有明显的差异。一个极端是肝脏，其中1c转录本以9：1的比例占优势。在小鼠肾上腺和脂肪组织以及人的肝脏和肾上腺中也发现了高1c：1a的比例。另一个极端是脾，其比例为1c：1a(1：10)。在五种不同的培养细胞系中，包括来自人肝细胞的HepG2系，1a转录本占主导地位(1c：1a比和lt；1：2)。在小鼠3T3-L1前脂肪细胞中，存在1a转录本，但未检测到1c转录本。当这些细胞在培养中通过激素处理分化为脂肪细胞时，1a转录物的数量显著增加(8.2倍)，而1c转录物几乎检测不到。我们的结论是，SREBP-1a和1c的转录本独立地受调节区控制，这些调节区对器官特异性和代谢因子做出不同的反应。
The 5' end of the mRNA-encoding sterol regulatory element binding protein-1 (SREBP-1) exists in two forms, designated 1a and 1c. The divergence 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. Here we show that the ratio of SREBP-1c to 1a transcripts varies markedly among organs of the adult mouse. At one extreme is the liver, in which the 1c transcript predominates by a 9:1 ratio. High 1c:1a ratios are also found in mouse adrenal gland and adipose tissue and in human liver and adrenal gland. At the other extreme is the spleen, which shows a reversed 1c:1a ratio (1:10). In five different lines of cultured cells, including the HepG2 line derived from human hepatocytes, the 1a transcript predominated (1c:1a ratio < 1:2). In mouse 3T3-L1 preadipocytes, the 1a transcript was present, but the 1c transcript was not detectable. When these cells were differentiated into adipocytes by hormone treatment in culture, the amount of 1a transcript rose markedly (8.2-fold), and the 1c transcript remained virtually undetectable. We conclude that the SREBP-1a and 1c transcripts are controlled independently by regulatory regions that respond differentially to organ-specific and metabolic factors.