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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 ( IF 1.4 ) Pub Date : 2019-06-10 , DOI: 10.1016/j.ghir.2019.06.002
Michael Wallis 1
Affiliation  

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 utilized 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.



中文翻译:

人胰岛素样生长因子I(IGF-1)基因中新剪接的5'外显子的表征,在肝脏和某些癌症中表达。

在哺乳动物中,大的IGF-I基因包含6个外显子,可以进行选择性剪接。所有的转录本均含有编码成熟IGF-1的外显子3和4,但其他外显子以各种组合形式包含在内,从而至少提供了6种可能的成熟mRNA。在5'端,外显子1和2与外显子3交替剪接,给出了不同的前导/信号序列。在这项研究中表明,在人类中,在外显子1的上游还存在一个额外的外显子(称为外显子0)。该外显子可以直接剪接到外显子3上,或者更不常见地剪接到外显子1上。外显子0用于肝脏,大约24%的IGF-I转录本在前列腺和子宫内膜中占很小的比例(<1%的转录本),但在其他29个正常人体组织中却没有。外显子0序列包括帧内ATG / AUG,可能提供翻译起点,从而为IGF-I前体提供非常长的信号肽。但是,该ATG非常靠近5'末端,可能未包含在所有转录本中;外显子3中的帧内ATG可以提供替代的起点。在其他猿类中检出了外显子0的利用,并在很小的程度上在旧世界的猴子中发现了,但在新世界的猴子,prosimians或各种非灵长类哺乳动物中却没有发现。外显子0在大多数人类肿瘤中均未表达,但在许多前列腺肿瘤中使用的水平远高于正常前列腺中所见的水平,而在肝肿瘤中使用的水平低于正常肝脏中的水平。在其他猿类中检出了外显子0的利用,并在很小的程度上在旧世界的猴子中发现了,但在新世界的猴子,prosimians或各种非灵长类哺乳动物中却没有发现。外显子0在大多数人类肿瘤中均未表达,但在许多前列腺肿瘤中使用的水平远高于正常前列腺中所见的水平,而在肝肿瘤中使用的水平低于正常肝脏中的水平。在其他猿类中检出了外显子0的利用,并在很小的程度上在旧世界的猴子中发现了,但在新世界的猴子,prosimians或各种非灵长类哺乳动物中却没有发现。外显子0在大多数人类肿瘤中均未表达,但在许多前列腺肿瘤中使用的水平远高于正常前列腺中所见的水平,而在肝肿瘤中使用的水平低于正常肝脏中的水平。

更新日期:2019-06-10
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