Darnell J C, Mostovetsky O, Darnell R B
Howard Hughes Medical Institute, The Rockefeller University, New York, NY, USA.
Genes Brain Behav. 2005 Aug;4(6):341-9. doi: 10.1111/j.1601-183X.2005.00144.x.
The Fragile X Syndrome is caused by the loss of function of the FMR1 gene (Pieretti et al. 1991. Cell 66, 817-822; O'Donnell & Warren 2002. Annu Rev Neurosci 25, 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 (Darnell et al. 2004 Ment Retard Dev Disabil Res Rev 10, 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.
脆性X综合征由FMR1基因功能缺失引起（皮耶雷蒂等人，1991年。《细胞》66卷，817 - 822页；奥唐纳和沃伦，2002年。《神经科学年度评论》25卷，315 - 338页）。鉴定FMRP结合的RNA靶标是理解该蛋白质功能及其缺失所导致细胞缺陷的关键步骤（达内尔等人，2004年。《智力迟钝与发育障碍研究评论》10卷，49 - 52页）。在此，我们讨论当前对FMRP作为一种RNA结合蛋白的理解、用于鉴定FMRP RNA靶标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在转染的神经母细胞瘤细胞中的多核糖体结合，但RGG框的缺失则不会。这表明FMRP的RGG框与RNA的结合可能介导细胞mRNA代谢的其他方面，如mRNA定位，或者它可能在多核糖体结合的下游发挥作用。
