FMRP RNA targets: identification and validation
FMRP RNA targets: identification and validation
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DOI：
10.1111/j.1601-183x.2005.00144.x
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发表时间：
2005-08-01
影响因子：
2.5
通讯作者：
Darnell, RB
中科院分区：
文献类型：
--
作者：
Darnell, JC;Mostovetsky, O;Darnell, RB
脆性 X 综合征是由 FMR1 基因功能丧失引起的（Pierettiet al. 1991.Cell66, 817–822；O'Donnell & Warren 2002.Annu Rev Neurosci25, 315–338]。鉴定 FMRP 结合的 RNA 靶点是了解该蛋白功能以及由于其缺失而导致的细胞缺陷的关键步骤（Darnellet） 等人。 2004Ment Retard Dev Disabil Res Rev10, 49–52)。在这里，我们讨论目前对 FMRP 作为 RNA 结合蛋白的理解、识别 FMRP RNA 靶标所采用的不同方法以及其中一些方法与 FMRP 生物学的相关性。此外，我们提供的证据表明，FMRP 的 K 同源 (KH)1 或 KH2 结构域中的点突变会消除其功能。 转染的神经母细胞瘤细胞中存在多核糖体关联，但 RGG 盒的删除则不然。这表明 FMRP 的 RGG 盒与 RNA 的结合可能介导细胞 mRNA 代谢的其他方面，例如 mRNA 定位，或者它可能在多核糖体关联的下游发挥作用。
The Fragile X Syndrome is caused by the loss of function of theFMR1gene (Pierettiet al. 1991.Cell66, 817–822; O'Donnell & Warren 2002.Annu Rev Neurosci25, 315–338]. Identification of the RNA targets to which FMRP binds is a key step in understanding the function of the protein and the cellular defects caused by its absence (Darnellet al. 2004Ment Retard Dev Disabil Res Rev10, 49–52). Here we discuss the current understanding of FMRP as an RNA‐binding protein, the different approaches that have been taken to identify FMRP RNA targets and the relevance of some of these approaches to FMRP biology. In addition, we present evidence that point mutations in the K‐homology (KH)1 or KH2 domains of FMRP abrogate its polyribosome association in transfected neuroblastoma cells but that the deletion of the RGG box does not. This suggests that RNA binding by the RGG box of FMRP may mediate other aspects of cellular mRNA metabolism such as mRNA localization or that it may have a role downstream of polyribosome association.