Fragile X related protein 1 isoforms differentially modulate the affinity of fragile X mental retardation protein for G-quartet RNA structure.
Fragile X related protein 1 isoforms differentially modulate the affinity of fragile X mental retardation protein for G-quartet RNA structure.
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DOI：
10.1093/nar/gkl1021
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发表时间：
2007
影响因子：
14.9
通讯作者：
Bardoni B
中科院分区：
文献类型：
--
作者：
Bechara E;Davidovic L;Melko M;Bensaid M;Tremblay S;Grosgeorge J;Khandjian EW;Lalli E;Bardoni B
脆性X综合征是遗传性智力低下的最常见形式，是由于缺乏脆性X智力低下蛋白（FMRP）的表达，FMRP是一种对G-四联体RNA结构具有高度特异性的RNA结合蛋白。FMRP参与mRNA代谢的几个步骤：核质运输，翻译控制和神经元中沿沿着运输。脆性X相关蛋白1（FXR 1 P）是FMRP的同源物和相互作用物，已被假定具有与FMRP类似的功能，导致其可以补偿脆性X患者中FMRP缺失的假设。在这里，我们分析了在不同组织中表达的FXR 1 P的三种亚型特异性结合G-四联体RNA结构的能力。发现只有最长的FXR 1 P同种型能够特异性结合G-四联体RNA，尽管与FMRP相比具有较低的亲和力，而其他两种同种型负调节FMRP对G-四联体RNA的亲和力。这一结果是重要的破译脆性X综合征的分子基础，通过理解FMRP的作用在其多分子复合物在不同组织的背景下。此外，我们发现FXR 1 P的作用是协同的，而不是补偿FMRP功能。
Fragile X syndrome, the most frequent form of inherited mental retardation, is due to the absence of expression of the Fragile X Mental Retardation Protein (FMRP), an RNA binding protein with high specificity for G-quartet RNA structure. FMRP is involved in several steps of mRNA metabolism: nucleocytoplasmic trafficking, translational control and transport along dendrites in neurons. Fragile X Related Protein 1 (FXR1P), a homologue and interactor of FMRP, has been postulated to have a function similar to FMRP, leading to the hypothesis that it can compensate for the absence of FMRP in Fragile X patients. Here we analyze the ability of three isoforms of FXR1P, expressed in different tissues, to bind G-quartet RNA structure specifically. Only the longest FXR1P isoform was found to be able to bind specifically the G-quartet RNA, albeit with a lower affinity as compared to FMRP, whereas the other two isoforms negatively regulate the affinity of FMRP for G-quartet RNA. This result is important to decipher the molecular basis of fragile X syndrome, through the understanding of FMRP action in the context of its multimolecular complex in different tissues. In addition, we show that the action of FXR1P is synergistic rather than compensatory for FMRP function.
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影响因子：
2.9
作者：
Dubé M;Huot ME;Khandjian EW
通讯作者：
Khandjian EW
影响因子：
4.8
作者：
Garnon, J;Lachance, C;Radzioch, D
通讯作者：
Radzioch, D
影响因子：
3.5
作者：
Mientjes, EJ;Willemsen, R;Nelson, DL
通讯作者：
Nelson, DL
影响因子：
11.4
作者：
Rackham, O;Brown, CM
通讯作者：
Brown, CM
影响因子：
2.5
作者：
Darnell, JC;Mostovetsky, O;Darnell, RB
通讯作者：
Darnell, RB