Characterization of a novel alternatively-spliced 5' exon in the human insulin-like growth factor I (IGF-I) gene, expressed in liver and some cancers

Wallis, Michael (2019) Characterization of a novel alternatively-spliced 5' exon in the human insulin-like growth factor I (IGF-I) gene, expressed in liver and some cancers. Growth Hormone and IGF Research, 46-47. pp. 36-43. ISSN 1096-6374

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Abstract

In mammals, the large IGF-I gene comprises 6 exons, which are subject to alternative splicing. All transcripts contain exons 3 and 4, encoding mature IGF-I, but the other exons are included in various combinations, giving at least 6 possible mature mRNAs. At the 5' end, exons 1 and 2 are spliced alternatively to exon 3, giving different leader/signal sequences. It is shown in this study that in human an additional exon (designated exon 0) is present, upstream of exon 1. This can be spliced directly to exon 3 or, less frequently, into exon 1. Exon 0 is utilised in liver, in about 24% of IGF-I transcripts, to a minor extent in prostate and endometrium (<1% of transcripts), but not in any of 29 other normal human tissues examined. The exon 0 sequence includes an in-frame ATG/AUG, potentially providing a translation start point giving an IGF-I precursor with a very long signal peptide. However, this ATG is very close to the 5' end, and may not be included in all transcripts; an in-frame ATG in exon 3 could provide an alternative start point. Utilization of exon 0 was detected in other apes, and to a small extent in Old World monkeys, but not in New World monkeys, prosimians or various non-primate mammals. Exon 0 was not expressed in most human tumours, but was utilized in many prostate tumours, at levels much greater than seen in normal prostate, and in liver tumours, at a lower level than in normal liver.

Item Type: Article
Keywords: IGF1, exon 0, alternative splicing, liver, primates, prostate cancer
Schools and Departments: School of Life Sciences > Biochemistry
Subjects: Q Science > QP Physiology > QP0501 Animal biochemistry
Depositing User: Michael Wallis
Date Deposited: 25 Jun 2019 12:32
Last Modified: 01 Jul 2019 11:46
URI: http://sro.sussex.ac.uk/id/eprint/84510

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