Kunz Meik, Xiao Ke, Liang Chunguang, Viereck Janika, Pachel Christina, Frantz Stefan, Thum Thomas, Dandekar Thomas
Functional Genomics and Systems Biology Group, Department of Bioinformatics, Biocenter, Würzburg, Germany; Institute for Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Hannover, Germany.
Institute for Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Hannover, Germany; Plant Breeding Institute, Christian-Albrechts-University of Kiel, Olshausenstr. 40, 24098 Kiel, Germany.
J Mol Cell Cardiol. 2015 Dec;89(Pt A):3-10. doi: 10.1016/j.yjmcc.2014.11.027. Epub 2014 Dec 5.
MicroRNAs (miRNAs) are small ~22 nucleotide non-coding RNAs and are highly conserved among species. Moreover, miRNAs regulate gene expression of a large number of genes associated with important biological functions and signaling pathways. Recently, several miRNAs have been found to be associated with cardiovascular diseases. Thus, investigating the complex regulatory effect of miRNAs may lead to a better understanding of their functional role in the heart. To achieve this, bioinformatics approaches have to be coupled with validation and screening experiments to understand the complex interactions of miRNAs with the genome. This will boost the subsequent development of diagnostic markers and our understanding of the physiological and therapeutic role of miRNAs in cardiac remodeling. In this review, we focus on and explain different bioinformatics strategies and algorithms for the identification and analysis of miRNAs and their regulatory elements to better understand cardiac miRNA biology. Starting with the biogenesis of miRNAs, we present approaches such as LocARNA and miRBase for combining sequence and structure analysis including phylogenetic comparisons as well as detailed analysis of RNA folding patterns, functional target prediction, signaling pathway as well as functional analysis. We also show how far bioinformatics helps to tackle the unprecedented level of complexity and systemic effects by miRNA, underlining the strong therapeutic potential of miRNA and miRNA target structures in cardiovascular disease. In addition, we discuss drawbacks and limitations of bioinformatics algorithms and the necessity of experimental approaches for miRNA target identification. This article is part of a Special Issue entitled 'Non-coding RNAs'.
微小RNA(miRNA)是一类长度约为22个核苷酸的非编码RNA,在物种间高度保守。此外,miRNA可调控大量与重要生物学功能和信号通路相关的基因表达。最近,已发现多种miRNA与心血管疾病有关。因此,研究miRNA的复杂调控作用可能有助于更好地理解它们在心脏中的功能作用。为实现这一目标,必须将生物信息学方法与验证和筛选实验相结合,以了解miRNA与基因组的复杂相互作用。这将推动后续诊断标志物的开发,并增进我们对miRNA在心脏重塑中的生理和治疗作用的理解。在这篇综述中,我们重点介绍并解释用于识别和分析miRNA及其调控元件的不同生物信息学策略和算法,以更好地理解心脏miRNA生物学。从miRNA的生物合成开始,我们介绍了诸如LocARNA和miRBase等方法,用于结合序列和结构分析,包括系统发育比较以及RNA折叠模式的详细分析、功能靶标预测、信号通路以及功能分析。我们还展示了生物信息学在多大程度上有助于应对miRNA带来的前所未有的复杂性和系统性影响,强调了miRNA及其靶标结构在心血管疾病中的强大治疗潜力。此外,我们讨论了生物信息学算法的缺点和局限性以及通过实验方法鉴定miRNA靶标的必要性。本文是名为“非编码RNA”的特刊的一部分。