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内含子 microRNAs 通过介导协同和拮抗的调节作用来支持其宿主基因。

Intronic microRNAs support their host genes by mediating synergistic and antagonistic regulatory effects.

机构信息

Institute of Bioinformatics and Systems Biology, CMB, Helmholtz Zentrum München, Germany.

出版信息

BMC Genomics. 2010 Apr 6;11:224. doi: 10.1186/1471-2164-11-224.

Abstract

BACKGROUND

MicroRNA-mediated control of gene expression via translational inhibition has substantial impact on cellular regulatory mechanisms. About 37% of mammalian microRNAs appear to be located within introns of protein coding genes, linking their expression to the promoter-driven regulation of the host gene. In our study we investigate this linkage towards a relationship beyond transcriptional co-regulation.

RESULTS

Using measures based on both annotation and experimental data, we show that intronic microRNAs tend to support their host genes by regulation of target gene expression with significantly correlated expression patterns. We used expression data of three differentiating cell types and compared gene expression profiles of host and target genes. Many microRNA target genes show expression patterns significantly correlated with the expressions of the microRNA host genes. By calculating functional similarities between host and predicted microRNA target genes based on GO annotations, we confirm that many microRNAs link host and target gene activity in an either synergistic or antagonistic manner.

CONCLUSIONS

These two regulatory effects may result from fine tuning of target gene expression functionally related to the host or knock-down of remaining opponent target gene expression. This finding allows to extend the common practice of mapping large scale gene expression data to protein associated genes with functionality of co-expressed intronic microRNAs.

摘要

背景

通过翻译抑制来控制基因表达的 microRNA 对细胞调控机制有重大影响。大约 37%的哺乳动物 microRNA 似乎位于蛋白质编码基因的内含子中,将它们的表达与启动子驱动的宿主基因调控联系起来。在我们的研究中,我们调查了这种联系是否超出了转录共调控的范围。

结果

我们使用基于注释和实验数据的度量方法,表明内含子 microRNA 倾向于通过调节靶基因表达来支持其宿主基因,这些靶基因具有显著相关的表达模式。我们使用三种分化细胞类型的表达数据,并比较了宿主和靶基因的表达谱。许多 microRNA 靶基因的表达模式与 microRNA 宿主基因的表达显著相关。通过基于 GO 注释计算宿主和预测的 microRNA 靶基因之间的功能相似性,我们证实许多 microRNA 以协同或拮抗的方式将宿主和靶基因的活性联系起来。

结论

这两种调节效应可能是通过对与宿主功能相关的靶基因表达进行微调,或者是通过敲低剩余的拮抗靶基因表达而产生的。这一发现使得将大规模基因表达数据映射到具有共表达内含子 microRNA 功能的蛋白质相关基因的常见做法得以扩展。

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