5091 Genetic Medicine Building, 120 Mason Farm Road, Department of Genetics, Lineberger Comprehensive Cancer Center, Carolina Center for Genome Sciences, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Curr Genomics. 2013 Mar;14(1):68-77. doi: 10.2174/138920213804999183.
Cellular gene expression is governed by a complex, multi-faceted network of regulatory interactions. In the last decade, microRNAs (miRNAs) have emerged as critical components of this network. miRNAs are small, non-coding RNA molecules that serve as post-transcriptional regulators of gene expression. Although there has been substantive progress in our understanding of miRNA-mediated gene regulation, the mechanisms that control the expression of the miRNAs themselves are less well understood. Identifying the factors that control miRNA expression will be critical for further characterizing miRNA function in normal physiology and pathobiology. We describe recent progress in the efforts to map genomic regions that control miRNA transcription (such as promoters). In particular, we highlight the utility of large-scale "-omic" data, such as those made available by the ENCODE and the NIH Roadmap Epigenomics consortiums, for the discovery of transcriptional control elements that govern miRNA expression. Finally, we discuss how integrative analysis of complementary genetic datasets, such as the NHGRI Genome Wide Association Studies Catalog, can predict novel roles for transcriptional mis-regulation of miRNAs in complex disease etiology.
细胞基因表达受一个复杂的、多方面的调控相互作用网络调控。在过去的十年中,microRNAs (miRNAs) 已成为该网络的关键组成部分。miRNAs 是小的、非编码 RNA 分子,作为基因表达的转录后调控因子。尽管我们对 miRNA 介导的基因调控有了实质性的进展,但控制 miRNA 自身表达的机制还不太清楚。确定控制 miRNA 表达的因素对于进一步描述 miRNA 在正常生理和病理生物学中的功能至关重要。我们描述了在绘制控制 miRNA 转录(如启动子)的基因组区域方面的最新进展。特别是,我们强调了大规模“-omic”数据(如 ENCODE 和 NIH Roadmap Epigenomics 联盟提供的数据)在发现控制 miRNA 表达的转录调控元件方面的应用。最后,我们讨论了如何综合分析互补的遗传数据集,如 NHGRI 全基因组关联研究目录,以预测 miRNA 转录失调在复杂疾病病因学中的新作用。