Interactions of the G quartet forming semaphorin 3F RNA with the RGG box domain of the fragile X protein family.
Interactions of the G quartet forming semaphorin 3F RNA with the RGG box domain of the fragile X protein family.
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DOI：
10.1093/nar/gkm581
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发表时间：
2007
影响因子：
14.9
通讯作者：
Mihailescu MR
中科院分区：
文献类型：
--
作者：
Menon L;Mihailescu MR
脆性X综合征是遗传性智力低下的最常见原因，它是由fmr1基因的转录沉默引起的，这是由于CGG三核苷酸重复的不稳定扩增及其随后在其5 ' UTR中的超甲基化。该基因编码脆性X智力迟钝蛋白（FMRP），这是一种RNA结合蛋白，已被证明使用其RGG盒结构域与G四分体形成RNA结合。在这项研究中，我们通过荧光、紫外和圆二色光谱等生物物理方法，详细分析了FMRP RGG盒结构域与其提出的RNA靶点之一——人类信号蛋白3F (S3F) RNA之间的相互作用。我们发现该RNA形成一个含G四重奏的结构，该结构被FMRP RGG盒以高亲和力和特异性识别。此外，我们还分析了人类S3F RNA与两种FMRP常染色体相似基因FXR1P和FXR2P的RGG盒和RG簇的相互作用。我们发现该RNA仅与FXR1P RGG盒结合具有高亲和力和特异性，而不与FXR2P RG簇结合。FMRP和FXR1P RGG box都能够解开S3F RNA的G四重奏结构，然而，该过程所需的肽浓度非常不同：RNA:FMRP RGG box的比例为1:6，而RNA:FXR1P RGG box的比例为1:2。
Fragile X syndrome, the most common cause of inherited mental retardation, is caused by the transcriptional silencing of the fmr1 gene due to an unstable expansion of a CGG trinucleotide repeat and its subsequent hypermethylation in its 5′ UTR. This gene encodes for the fragile X mental retardation protein (FMRP), an RNA-binding protein that has been shown to use its RGG box domain to bind to G quartet-forming RNA. In this study, we performed a detailed analysis of the interactions between the FMRP RGG box domain and one of its proposed RNA targets, human semaphorin 3F (S3F) RNA by using biophysical methods such as fluorescence, UV and circular dichroism spectroscopy. We show that this RNA forms a G quartet-containing structure, which is recognized with high affinity and specificity by the FMRP RGG box. In addition, we analyzed the interactions of human S3F RNA with the RGG box and RG cluster of the two FMRP autosomal paralogs, the FXR1P and FXR2P. We found that this RNA is bound with high affinity and specificity only by the FXR1P RGG box, but not by the FXR2P RG cluster. Both FMRP and FXR1P RGG box are able to unwind the G quartet structure of S3F RNA, however, the peptide concentrations required in this process are very different: a ratio of 1:6 RNA:FMRP RGG box versus 1:2 RNA:FXR1P RGG box.
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影响因子：
5.6
作者：
Kelly, JA;Feigon, J;Yeates, TO
通讯作者：
Yeates, TO
影响因子：
5.6
作者：
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DOI：
10.1073/pnas.89.18.8832
发表时间：
1992-09-15
影响因子：
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作者：
JIN, RZ;GAFFNEY, BL;BRESLAUER, KJ
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作者：
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通讯作者：
Bardoni B
影响因子：
5.6
作者：
Matsugami, A;Ouhashi, K;Katahira, M
通讯作者：
Katahira, M