NMR structure of the let-7 miRNA interacting with the site LCS1 of lin-41 mRNA from Caenorhabditis elegans.
NMR structure of the let-7 miRNA interacting with the site LCS1 of lin-41 mRNA from Caenorhabditis elegans.
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DOI：
10.1093/nar/gkq640
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发表时间：
2010-11
影响因子：
14.9
通讯作者：
Plavec J
中科院分区：
文献类型：
--
作者：
Cevec M;Thibaudeau C;Plavec J
我们已经确定了一个34-nt RNA构建体的三维结构，在此命名为LCS 1co，它模拟了let-7 microRNA（miRNA）与lin-41 mRNA 3′-非翻译区中的一个互补结合位点LCS 1的相互作用。let-7 miRNA控制线虫秀丽隐杆线虫的发育时间，并且在哺乳动物中高度保守。lin-41 mRNA 3′-非翻译区两个保守的let-7互补位点LCS 1和LCS 2的序列和结构对于lin-41的适当下调是重要的。高分辨率NMR结构揭示了let-7 miRNA与lin-41 mRNA结合的细节，这涉及在种子区域内形成具有非典型结构元件的复合物。LCS 1co具有茎环结构，包括两个茎、一个不对称的内环和一个腺嘌呤凸起。与涉及LCS 2结合位点的let-7：lin-41复合物的NMR溶液状态结构的比较表明，与LCS 2co的明确定义的不对称环相比，LCS 1co的不对称内环的构象自由度与上下茎之间较小的弯曲相关。
We have determined the 3D structure of a 34-nt RNA construct, herein named LCS1co, which mimics the interaction of let-7 microRNA (miRNA) to one of its complementary binding sites, LCS1, in the 3′-untranslated region of lin-41 mRNA by solution-state NMR spectroscopy. let-7 miRNAs control the timing of development of the nematode Caenorhabditis elegans and are highly conserved in mammals. The sequence and structure of the two conserved let-7 complementary sites, LCS1 and LCS2, in the 3′-untranslated region of lin-41 mRNA are important for a proper downregulation of lin-41. The high-resolution NMR structure reveals details of the binding of let-7 miRNA to lin-41 mRNA which involves formation of a complex with non-canonical structural elements within the seed region. LCS1co exhibits a stem-loop structure with two stems, an asymmetric internal loop and an adenine bulge. Comparison with the NMR solution-state structure of the let-7:lin-41 complex involving the LCS2-binding site shows that conformational freedom of the asymmetric internal loop of LCS1co correlates with a smaller bend between the upper and lower stems in comparison to the well-defined asymmetric loop of LCS2co.
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