Specificity of microRNA target selection in translational repression

Specificity of microRNA target selection in translational repression
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DOI:
10.1101/gad.1184404
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发表时间:
2004-03-01
影响因子:
10.5
通讯作者:
Sharp, PA
Sharp, PA
中科院分区:
生物学1区
文献类型:
--
作者:
Doench, JG;Sharp, PA

文献摘要

被引文献

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microRNAs(miRNAs)是一类存在于植物和哺乳动物等进化上遥远的生物体中的非编码RNA,但它们调节的大多数mRNA是未知的。在这里,我们表明,一个miRNA的抑制靶mRNA的能力,在很大程度上取决于前8个核苷酸在5'区的miRNA的结合自由能。然而,该区域的G:U摆动碱基配对干扰的活性超出了基于热力学稳定性预测的范围。此外,mRNA可以同时被一种以上的miRNA抑制。达到的抑制水平取决于mRNA的量和可用的miRNA复合物的量。因此,预测的miRNA:mRNA相互作用必须在其他潜在相互作用和细胞条件的背景下进行观察。
MicroRNAs (miRNAs) are a class of noncoding RNAs found in organisms as evolutionarily distant as plants and mammals, yet most of the mRNAs they regulate are unknown. Here we show that the ability of an miRNA to translationally repress a target mRNA is largely dictated by the free energy of binding of the first eight nucleotides in the 5' region of the miRNA. However, G:U wobble base-pairing in this region interferes with activity beyond that predicted on the basis of thermodynamic stability. Furthermore, an mRNA can be simultaneously repressed by more than one miRNA species. The level of repression achieved is dependent on both the amount of mRNA and the amount of available miRNA complexes. Thus, predicted miRNA:mRNA interactions must be viewed in the context of other potential interactions and cellular conditions.