Functional and evolutionary significance of human microRNA seed region mutations.

Functional and evolutionary significance of human microRNA seed region mutations.
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DOI:
10.1371/journal.pone.0115241
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
McDonald JF
McDonald JF
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Hill CG;Jabbari N;Matyunina LV;McDonald JF

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近年来,在正常和疾病细胞中,microRNAs已经成为细胞功能的重要调节者。MiRNAs通过mRNA降解和/或翻译抑制来协调调节大量的靶基因。动物miRNAs的信使核糖核酸靶标主要编码在分子5‘端2-8位的7个核苷酸的“种子区”内。在这里,我们结合计算分析和实验研究来探索人类miRNAs种子区域内序列变异的功能意义。结果表明,即使在种子区内替换一个核苷酸,也会使信使核糖核酸靶标的谱改变50%。即使是种子区内单核苷酸变化的高功能成本也与其在物种内和物种间的miRNA家族之间的高序列保守性相一致,并表明可能是miRNA调控进化的基础过程。
MicroRNAs have emerged in recent years as important regulators of cell function in both normal and diseased cells. MiRNAs coordinately regulate large suites of target genes by mRNA degradation and/or translational inhibition. The mRNA target specificities of miRNAs in animals are primarily encoded within a 7 nt “seed region” mapping to positions 2–8 at the molecule's 5′ end. We here combine computational analyses with experimental studies to explore the functional significance of sequence variation within the seed region of human miRNAs. The results indicate that a substitution of even a single nucleotide within the seed region changes the spectrum of mRNA targets by >50%. The high functional cost of even single nucleotide changes within seed regions is consistent with their high sequence conservation among miRNA families both within and between species and suggests processes that may underlie the evolution of miRNA regulatory control.
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