Species-specific and isoform-specific RNA binding of human and mouse fragile X mental retardation proteins
Species-specific and isoform-specific RNA binding of human and mouse fragile X mental retardation proteins
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DOI：
10.1006/bbrc.2002.6768
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发表时间：
2002-04-12
影响因子：
3.1
通讯作者：
Sung, YJ
中科院分区：
文献类型：
--
作者：
Denman, RB;Sung, YJ
脆性X RNA结合蛋白FMRP的缺失导致人类的巨睾丸症和智力迟钝。小鼠直系同源物的发现导致了几种FMRP敲除小鼠品系的发展，这些小鼠品系重现了该疾病的一些特征。由于小鼠和人的FMRP在其RNA结合结构域中的几个氨基酸上不同，我们比较了这两种直系同源物的RNA结合谱。五个变体FMRP，其差异产生的选择性剪接和保守的RNA结合结构域内的突变，进行了检查。同聚物结合研究表明，人FMRP（hFMRP）结合范围更广的单链模拟物比小鼠FMRP（mFMRP），这些相互作用是复杂的和合作的。hFMRP和mFMRP也显示出对结合其自身mRNA的显著偏好，具体地，我们发现mFMRP同种型比其人类对应物更紧密地结合mFMR1 mRNA。最后，这些数据表明，每个FMRP变体独特地结合RNA，导致一组具有不同亲和力的蛋白质。(C)2002 Elsevier Science（美国）。
The loss of the fragile X RNA binding protein, FMRP, causes macroorchidism and mental retardation in man. The discovery of a mouse ortholog led to the development of several FMRP knockout mouse strains that recapitulate some features of the disease. As mouse and human FMRPs differ in several amino acids in their RNA binding domains, we compared the RNA binding profiles of these two orthologs. Five variant FMRPs, whose differences arose from alternative splicing and mutation within the conserved RNA binding domains, were examined. Homoribopolymer binding studies showed that human FMRPs (hFMRP) bound a broader range of single-stranded mimetics than mouse FMRPs (mFMRP) and these interactions were both complex and cooperative. hFMRP and mFMRP also displayed significant preferences toward binding their own mRNA, specifically we found that the mFMRP isoforms bind mFMR1 mRNA much more tightly than their human counterparts. Finally, these data demonstrate that each FMRP variant binds RNAs uniquely, resulting in a set of proteins with differing affinities. (C) 2002 Elsevier Science (USA).