Cell-type-specific signatures of microRNAs on target mRNA expression
Cell-type-specific signatures of microRNAs on target mRNA expression
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DOI：
10.1073/pnas.0511045103
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发表时间：
2006-02-21
影响因子：
11.1
通讯作者：
Rajewsky, N
中科院分区：
文献类型：
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作者：
Sood, P;Krek, A;Rajewsky, N
尽管已知人类基因组包含数百个microRNA（miRNA）基因，并且每个miRNA可以调节大量mRNA靶标，但miRNA对mRNA组织谱的总体影响尚未系统地阐明。在这里，我们表明，几种高度组织特异性的miRNA的预测的人类mRNA靶标通常在与miRNA相同的组织中表达，但其水平显著低于不存在miRNA的组织。相反，高表达的基因通常富含不具有在这些组织中表达的miRNA的识别基序的mRNA。总之，我们的数据支持这样的假设，即在许多人体组织中，miRNA表达广泛地有助于mRNA表达的组织特异性。基于这些见解，我们应用计算工具将3'UTR基序与miRNA过表达或敲低后mRNA水平的变化直接关联。我们表明，该工具可以识别功能重要的3' UTR基序，而无需跨物种比较。
Although it is known that the human genome contains hundreds of microRNA (miRNA) genes and that each miRNA can regulate a large number of mRNA targets, the overall effect of miRNAs on mRNA tissue profiles has not been systematically elucidated. Here, we show that predicted human mRNA targets of several highly tissue-specific miRNAs are typically expressed in the same tissue as the miRNA but at significantly lower levels than in tissues where the miRNA is not present. Conversely, highly expressed genes are often enriched in mRNAs that do not have the recognition motifs for the miRNAs expressed in these tissues. Together, our data support the hypothesis that miRNA expression broadly contributes to tissue specificity of mRNA expression in many human tissues. Based on these insights, we apply a computational tool to directly correlate 3' UTR motifs with changes in mRNA levels upon miRNA overexpression or knockdown. We show that this tool can identify functionally important 3' UTR motifs without cross-species comparison.