Regulation of start site usage in the leader exons of the rat insulin-like growth factor-i gene by development, fasting, and diabetes

Martin L Adamo, Haya Ben-Hur, Charles T. Roberts, Derek LeRoith

Research output: Contribution to journalArticle

134 Citations (Scopus)

Abstract

Rat insulin-like growth factor-I (IGF-I) mRNAs with different 5'-untranslated region/prepeptide coding sequences result from transcription initiation in one of two leader exons. While not altering the mature IGF-I coding sequence, these different leaders potentially encode two distinct IGF-I prepeptides, one of 48 amino acids (exon 1) and one of 32 amino acids (exon 2). Within exon 1, transcription initiation is dispersed (Le. occurs over a ~350-basepair region), while within exon 2, it is highly localized. A fourth exon 1 start site, residing only approximately 30 basepairs from its 3' end, is suggested on the basis of RNase protection assays; its use would produce an mRNA encoding a third distinct IGF-I leader peptide of 22 amino acids. We have determined that during postnatal development, and as a result of insulinopenic diabetes and fasting, choice of transcription start sites within exon 1 in the liver is coordinately regulated, Le. use of all start sites increased during development and decreased in the two catabolic states. Transcription initiation at the single major site within exon 2 was also reduced in diabetes and fasting. Insulin replacement therapy and refeeding restored the levels of all transcripts coordinately. During postnatal development, however, transcripts initiating within exon 2 exhibited a different developmental profile than did exon 1 transcripts, increasing especially at the onset of GH-dependent linear growth. In liver, therefore, negative regulation of exon 1 and exon 2 transcription start site usage occurs in catabolic states, while in development, differential regulation of exon I and exon 2 transcription start sites occurs.

Original languageEnglish (US)
Pages (from-to)1677-1686
Number of pages10
JournalMolecular Endocrinology
Volume5
Issue number11
StatePublished - 1991
Externally publishedYes

Fingerprint

Somatomedins
Exons
Fasting
Genes
Insulin-Like Growth Factor I
Transcription Initiation Site
Amino Acids
Messenger RNA
5' Untranslated Regions
Liver
Ribonucleases
Protein Sorting Signals

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism

Cite this

Regulation of start site usage in the leader exons of the rat insulin-like growth factor-i gene by development, fasting, and diabetes. / Adamo, Martin L; Ben-Hur, Haya; Roberts, Charles T.; LeRoith, Derek.

In: Molecular Endocrinology, Vol. 5, No. 11, 1991, p. 1677-1686.

Research output: Contribution to journalArticle

Adamo, Martin L ; Ben-Hur, Haya ; Roberts, Charles T. ; LeRoith, Derek. / Regulation of start site usage in the leader exons of the rat insulin-like growth factor-i gene by development, fasting, and diabetes. In: Molecular Endocrinology. 1991 ; Vol. 5, No. 11. pp. 1677-1686.
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