Potent effect of target structure on microRNA function

Potent effect of target structure on microRNA function
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DOI:
10.1038/nsmb1226
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发表时间:
2007-04-01
影响因子:
16.8
通讯作者:
Ding, Ye
Ding, Ye
中科院分区:
生物学1区
文献类型:
--
作者:
Long, Dang;Lee, Rosalind;Ding, Ye

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microRNA(miRNA)是小的非编码RNA,通过与靶标元素RNA结合来抑制蛋白质合成。我们研究了目标二级结构对miRNA抑制功效的影响。使用SFOLD程序预测的结构,我们将miRNA与目标之间的相互作用建模为两步杂交反应:可访问的目标位点的成核,然后是混合延伸以破坏局部目标二级结构,并形成完整的miRNA-targoget uplex uplex uplex uplex uplexe 。该模型准确地说明了秀丽隐杆线虫lin-41 3'未翻译区域的各种突变形式对抑制的敏感性,以及在秀丽隐杆线虫和果蝇中的其他实验测试的mirna-target相互作用。这些发现表明,目标结构对miRNA的靶标识别产生了有效的影响,并建立了基于结构的全基因组鉴定动物miRNA靶标的框架。
MicroRNAs (miRNAs) are small noncoding RNAs that repress protein synthesis by binding to target messenger RNAs. We investigated the effect of target secondary structure on the efficacy of repression by miRNAs. Using structures predicted by the Sfold program, we model the interaction between an miRNA and a target as a two-step hybridization reaction: nucleation at an accessible target site followed by hybrid elongation to disrupt local target secondary structure and form the complete miRNA-target duplex. This model accurately accounts for the sensitivity to repression by let-7 of various mutant forms of the Caenorhabditis elegans lin-41 3' untranslated region and for other experimentally tested miRNA-target interactions in C. elegans and Drosophila melanogaster. These findings indicate a potent effect of target structure on target recognition by miRNAs and establish a structure-based framework for genome-wide identification of animal miRNA targets.