Insight into microRNA regulation by analyzing the characteristics of their targets in humans.
Insight into microRNA regulation by analyzing the characteristics of their targets in humans.
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DOI：
10.1186/1471-2164-10-594
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发表时间：
2009-12-10
期刊：
影响因子：
4.4
通讯作者：
Hu Z
中科院分区：
文献类型：
--
作者：
Hu Z
microRNA（miRNAs）被认为通过转录后基因调控来调节其靶点，并具有通过多种机制沉默基因表达的潜力。尽管以前的进展miRNA调控基因表达，很少有研究从基因组规模。为了获得对人类miRNA调节的新见解，我们使用大规模数据并进行了一系列研究，将miRNA靶基因的各种特征与非miRNA靶基因的各种特征进行比较。我们观察到miRNA和非miRNA靶基因在许多特征上存在显著差异，包括更高和更广泛的mRNA表达，更快的mRNA衰减速率，更长的蛋白质半衰期和更长的基因结构。基于这些特征，并通过分析它们之间的关系，我们发现，miRNA靶基因，除了具有miRNA抑制，最有可能是在更复杂的调控下比非miRNA靶基因，这是由它们的更高和更广泛的基因表达，但更长的基因结构证明。我们的基因表达更高、更广泛，但mRNA衰减率更快的结果也提供了证据，表明miRNA抑制先前存在的转录本的输出有助于更快速、更稳健地过渡到新的表达程序。这可以通过多个miRNA靶向的累加效应增强mRNA降解来实现。对miRNA靶基因性质的基因组规模分析揭示了miRNA调控人类基因表达的一般机制。这项研究的结果还表明，miRNA靶基因，除了具有miRNA抑制，是在更复杂的基因调控下比非miRNA靶基因。这些发现为miRNA调控人类基因表达提供了新的见解。
microRNAs (miRNAs) are believed to regulate their targets through posttranscriptional gene regulation and have the potential to silence gene expression via multiple mechanisms. Despite previous advances on miRNA regulation of gene expression, little has been investigated from a genome scale. To gain new insight into miRNA regulation in humans, we used large scale data and carried out a series of studies to compare various features of miRNA target genes to that of non-miRNA target genes. We observed significant differences between miRNA and non-miRNA target genes for a number of characteristics, including higher and broader mRNA expression, faster mRNA decay rate, longer protein half-life, and longer gene structures. Based on these features and by analyzing their relationships we found that miRNA target genes, other than having miRNA repression, were most likely under more complex regulation than non-miRNA target genes, which was evidenced by their higher and broader gene expression but longer gene structures. Our results of higher and broader gene expression but fast mRNA decay rates also provide evidence that miRNA dampening of the output of preexisting transcripts facilitates a more rapid and robust transition to new expression programs. This could be achieved by enhancing mRNA degradation through an additive effect from multiple miRNA targeting. Genome-scale analysis on the nature of miRNA target genes has revealed a general mechanism for miRNA regulation of human gene expression. The results of this study also indicate that miRNA target genes, other than having miRNA repression, are under more complex gene regulation than non-miRNA target genes. These findings provide novel insight into miRNA regulation of human gene expression.
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