Evolution of insulin-like growth factor II: characterization of the mouse IGF-II gene and identification of two pseudo-exons.
We have cloned the mouse insulin-like growth factor II (IGF-II) gene as a series of overlapping cosmid and lambda recombinants and have characterized its six exons. The gene extends over approximately 12 kb of mouse chromosome 7 and is located 18 kb 3' to the insulin 2 gene and in the same transcriptional polarity. Exons 1-3 encode distinct 5' untranslated regions and are transcribed by three different promoters, P1, P2, and P3, into three IGF-II mRNAs sharing common coding and 3' untranslated sequences. Promoters P2 and P3 each contain a TATA box and appear to direct transcription from single initiation sites. By contrast, exon 1 has three major transcriptional start sites distributed over 556 nucleotides, and P1 lacks a TATA region and other typical transcriptional control sequences. Exons 4-6 code for the 180-amino-acid IGF-II precursor, and exon 6 also contains a 3,045-nucleotide 3' untranslated region which ends at a single polyadenylation site. In addition to six functional IGF-II exons, we identified two 5' "pseudo-exons," which appear to be evolutionarily retained remnants of an alternative promoter-exon cassette that is active in human IGF-II. Loss of the homolog of this promoter, which directs "adult-specific" expression of the IGF-II gene in some human tissues, may explain the disappearance of this growth factor from most murine tissues in the early postnatal period.
Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110.
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Rotwein
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Hall
D000595:Amino Acid Sequence; D000818:Animals; D001345:Autoradiography; D001483:Base Sequence; D015152:Blotting, Northern; D004247:DNA / Q000032:analysis; D005091:Exons; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D012313:RNA / Q000032:analysis; D012333:RNA, Messenger / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic
D012333:RNA, Messenger; D012313:RNA; D007335:Insulin-Like Growth Factor II; D004247:DNA