Differential expression of exons 1a and 1c in mRNAs for sterol regulatory element binding protein-1 in human and mouse organs and cultured cells

Iichiro Shimomura, Hitoshi Shimano, Jay D. Horton, Joseph L. Goldstein, Michael S. Brown

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586 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)838-845
Number of pages8
JournalJournal of Clinical Investigation
Volume99
Issue number5
StatePublished - Mar 1 1997

Fingerprint

Sterol Regulatory Element Binding Protein 1
Exons
Cultured Cells
Messenger RNA
Adrenal Glands
Nucleic Acid Regulatory Sequences
Transcription Initiation Site
Liver
Adipocytes
Adipose Tissue
Hepatocytes
Spleen
Hormones

Keywords

  • adipocytes
  • alternative splicing
  • cholesterol
  • fatty acids
  • liver
  • SREBP-1

ASJC Scopus subject areas

  • Medicine(all)

Cite this

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title = "Differential expression of exons 1a and 1c in mRNAs for sterol regulatory element binding protein-1 in human and mouse organs and cultured cells",
abstract = "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.",
keywords = "adipocytes, alternative splicing, cholesterol, fatty acids, liver, SREBP-1",
author = "Iichiro Shimomura and Hitoshi Shimano and Horton, {Jay D.} and Goldstein, {Joseph L.} and Brown, {Michael S.}",
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T1 - Differential expression of exons 1a and 1c in mRNAs for sterol regulatory element binding protein-1 in human and mouse organs and cultured cells

AU - Shimomura, Iichiro

AU - Shimano, Hitoshi

AU - Horton, Jay D.

AU - Goldstein, Joseph L.

AU - Brown, Michael S.

PY - 1997/3/1

Y1 - 1997/3/1

N2 - 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.

AB - 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.

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