Two isoforms of the mRNA binding protein IGF2BP2 are generated by alternative translational initiation.
Two isoforms of the mRNA binding protein IGF2BP2 are generated by alternative translational initiation.
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DOI：
10.1371/journal.pone.0033140
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Siddle K
中科院分区：
文献类型：
--
作者：
Le HT;Sorrell AM;Siddle K
IGF2BP2是mRNA结合蛋白家族的一员，在哺乳动物细胞中已被证明可以结合几种不同的mRNA，包括编码胰岛素样生长因子-2的mRNA之一。Igf2bp2基因多态性与发生2型糖尿病的风险相关，但缺乏Igf2bp2蛋白的详细功能特征。通过使用c端反应性抗体进行免疫印迹，我们在人和啮齿类动物中鉴定出一种新的IGF2BP2亚型，其分子量为58 kDa，其表达水平略低于全长65 kDa蛋白。我们通过诱变证明该异构体是由内部Met69的替代翻译起始产生的。它缺乏一个保守的n端RNA识别基序（RRM），预计在功能上与规范的全长同种异构体不同。我们进一步利用5′-RACE扩增cDNA来研究IGF2BP2 mRNA转录物。我们在主要翻译起始位点上游仅50-90 nts的高度保守区域发现了人类、小鼠和大鼠Igf2bp2基因的多个转录起始位点，排除了n端延伸异构体的存在。我们得出结论，在考虑细胞功能时应考虑IGF2BP2蛋白的结构异质性。
IGF2BP2 is a member of a family of mRNA binding proteins that, collectively, have been shown to bind to several different mRNAs in mammalian cells, including one of the mRNAs encoding insulin-like growth factor-2. Polymorphisms in the Igf2bp2 gene are associated with risk of developing type 2 diabetes, but detailed functional characterisation of IGF2BP2 protein is lacking. By immunoblotting with C-terminally reactive antibodies we identified a novel IGF2BP2 isoform with a molecular weight of 58 kDa in both human and rodents, that is expressed at somewhat lower levels than the full-length 65 kDa protein. We demonstrated by mutagenesis that this isoform is generated by alternative translation initiation at the internal Met69. It lacks a conserved N-terminal RNA Recognition Motif (RRM) and would be predicted to differ functionally from the canonical full length isoform. We further investigated IGF2BP2 mRNA transcripts by amplification of cDNA using 5′-RACE. We identified multiple transcription start sites of the human, mouse and rat Igf2bp2 genes in a highly conserved region only 50–90 nts upstream of the major translation start site, ruling out the existence of N-terminally extended isoforms. We conclude that structural heterogeneity of IGF2BP2 protein should be taken into account when considering cellular function.
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DOI：
10.1083/jcb.108.2.229
发表时间：
1989-02
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kozak M
通讯作者：
Kozak M
影响因子：
6.9
作者：
Li, Xia;Allayee, Hooman;Xiang, Anny H.;Trigo, Enrique;Hartiala, Jaana;Lawrence, Jean M.;Buchanan, Thomas A.;Watanabe, Richard M.
通讯作者：
Watanabe, Richard M.
影响因子：
5.3
作者：
Hansen, TVO;Hammer, NA;Nielsen, FC
通讯作者：
Nielsen, FC
影响因子：
2.6
作者：
Crocoll, A;Blum, M;Cato, ACB
通讯作者：
Cato, ACB
影响因子：
4.5
作者：
Hogg, J. Robert;Collins, Kathleen
通讯作者：
Collins, Kathleen