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VGF基因的结构,VGF是一种神经系统特异性mRNA,在PC12细胞中可被神经生长因子快速且选择性地诱导产生。

Structure of the gene encoding VGF, a nervous system-specific mRNA that is rapidly and selectively induced by nerve growth factor in PC12 cells.

作者信息

Salton S R, Fischberg D J, Dong K W

机构信息

Fishberg Research Center in Neurobiology, Mount Sinai School of Medicine, New York, New York 10029.

出版信息

Mol Cell Biol. 1991 May;11(5):2335-49. doi: 10.1128/mcb.11.5.2335-2349.1991.

Abstract

Nerve growth factor (NGF) plays a critical role in the development and survival of neurons in the peripheral nervous system. Following treatment with NGF but not epidermal growth factor, rat pheochromocytoma (PC12) cells undergo neural differentiation. We have cloned a nervous system-specific mRNA, NGF33.1, that is rapidly and relatively selectively induced by treatment of PC12 cells with NGF and basic fibroblast growth factor in comparison with epidermal growth factor. Analysis of the nucleic acid and predicted amino acid sequences of the NGF33.1 cDNA clone suggested that this clone corresponded to the NGF-inducible mRNA called VGF (A. Levi, J. D. Eldridge, and B. M. Paterson, Science 229:393-395, 1985; R. Possenti, J. D. Eldridge, B. M. Paterson, A. Grasso, and A. Levi, EMBO J. 8:2217-2223, 1989). We have used the NGF33.1 cDNA clone to isolate and characterize the VGF gene, and in this paper we report the complete sequence of the VGF gene, including 853 bases of 5' flank revealed TATAA and CCAAT elements, several GC boxes, and a consensus cyclic AMP response element-binding protein binding site. The VGF promoter contains sequences homologous to other NGF-inducible, neuronal promoters. We further show that VGF mRNA is induced in PC12 cells to a greater extent by depolarization and by phorbol-12-myristate-13-acetate treatment than by 8-bromo-cyclic AMP treatment. By Northern (RNA) and RNase protection analysis, VGF mRNA is detectable in embryonic and postnatal central and peripheral nervous tissues but not in a number of nonneural tissues. In the cascade of events which ultimately leads to the neural differentiation of NGF-treated PC12 cells, the VGF gene encodes the most rapidly and selectively regulated, nervous-system specific mRNA yet identified.

摘要

神经生长因子(NGF)在周围神经系统神经元的发育和存活中起着关键作用。用NGF而非表皮生长因子处理后,大鼠嗜铬细胞瘤(PC12)细胞会发生神经分化。我们克隆了一种神经系统特异性mRNA,即NGF33.1,与表皮生长因子相比,用NGF和碱性成纤维细胞生长因子处理PC12细胞后,该mRNA会迅速且相对选择性地被诱导。对NGF33.1 cDNA克隆的核酸和预测氨基酸序列分析表明,该克隆对应于名为VGF的NGF诱导型mRNA(A. Levi、J. D. Eldridge和B. M. Paterson,《科学》229:393 - 395,1985;R. Possenti、J. D. Eldridge、B. M. Paterson、A. Grasso和A. Levi,《欧洲分子生物学组织杂志》8:2217 - 2223,1989)。我们已使用NGF33.1 cDNA克隆分离并鉴定了VGF基因,在本文中我们报告了VGF基因的完整序列,包括5'侧翼的853个碱基,其中揭示了TATAA和CCAAT元件、几个GC框以及一个共有环磷酸腺苷反应元件结合蛋白结合位点。VGF启动子包含与其他NGF诱导型神经元启动子同源的序列。我们进一步表明,与8 - 溴环磷酸腺苷处理相比,去极化和佛波醇 - 12 - 肉豆蔻酸酯 - 13 - 乙酸酯处理在PC12细胞中诱导VGF mRNA的程度更高。通过Northern(RNA)和核糖核酸酶保护分析,在胚胎期和出生后的中枢和周围神经组织中可检测到VGF mRNA,但在许多非神经组织中未检测到。在最终导致用NGF处理的PC12细胞发生神经分化的一系列事件中,VGF基因编码了迄今已鉴定的调控最迅速且最具选择性的神经系统特异性mRNA。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/568d/359984/7505ed840474/molcellb00139-0013-a.jpg

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