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IGF1 Alternate splicing paper(rev2) with Figs.pdf (716.25 kB)

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

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posted on 2023-06-09, 18:10 authored by Michael Wallis
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.

History

Publication status

  • Published

File Version

  • Accepted version

Journal

Growth Hormone and IGF Research

ISSN

1096-6374

Publisher

Elsevier

Volume

46-47

Page range

36-43

Department affiliated with

  • Biochemistry Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2019-06-25

First Open Access (FOA) Date

2020-06-10

First Compliant Deposit (FCD) Date

2019-06-25

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