NF1 mRNA isoform expression in PC12 cells: Modulation by extrinsic factors

NF1 mRNA isoform expression in PC12 cells: Modulation by extrinsic factors
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DOI:
10.1006/excr.1996.0297
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发表时间:
1996-10-10
影响因子:
3.7
通讯作者:
Skuse, GR
Skuse, GR
中科院分区:
医学3区
文献类型:
--
作者:
Metheny, LJ;Skuse, GR

文献摘要

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大鼠神经纤维瘤病I型(NF 1)基因表达几种转录异构体,其不同之处在于编码GTP酶激活蛋白相关结构域的区域中外显子23 a和23 b的选择性剪接。这种选择性剪接事件的意义尚不清楚,影响异构体表达的因素在很大程度上是未知的。在这里,我们表明,各种因素可以调节这些异构体在PC12细胞中的表达。神经生长因子和地塞米松导致I型亚型增加,同时细胞增殖减少。地塞米松对I型同种型的上调以RNA合成依赖性方式发生。环己酰亚胺处理导致检测到被鉴定为鼠III型转录物的其他物种。这些结果表明,NF 1选择性剪接事件可以响应环境线索。NF 1转录本表达类型的变化可能在神经纤维蛋白的正常生理调节中起重要作用,并可能调节其在分化和增殖中的作用。(C)出版社:Academic Press,Inc.
The rat neurofibromatosis type I (NF1) gene expresses several transcript isoforms which differ by the alternative splicing of exons 23a and 23b in the region encoding the GTPase-activating protein-related domain. The significance of this alternative splicing event is unclear and the factors which influence isoform expression are largely unknown. Here we show that variety of factors can modulate the expression of these isoforms in PC12 cells. Nerve growth factor and dexamethasone lead to an increase in the type I isoform concurrent with a decrease in cellular proliferation. Upregulation of the type I isoform by dexamethasone occurs in an RNA synthesis-dependent manner. Cycloheximide treatment leads to the detection of an additional species identified as the murine type III transcript. These results suggest that the NF1 alternative splicing event can respond to environmental cues. The changes in the type of NF1 transcript expressed may be important in the normal physiological regulation of neurofibromin and may modulate its role in differentiation and proliferation. (C) 1996 Academic Press, Inc.