School of Biomedical Sciences and Pharmacy, Faculty of Health and Hunter Medical Research Institute, University of Newcastle, Callaghan, NSW, Australia.
Wiley Interdiscip Rev RNA. 2014 May-Jun;5(3):361-79. doi: 10.1002/wrna.1217. Epub 2014 Jan 23.
In recent times, microRNA (miRNA) have emerged as primary regulators of fundamental biological processes including cellular differentiation, proliferation, apoptosis, as well as synaptic plasticity. However, miRNAs bind their targets with only partial complementarity, making it very challenging to determine exactly how a miRNA is functioning in specific biological environments. This review discusses key principles of miRNA target recognition and function which have emerged through the progressive advancement of biological and bioinformatics approaches. Ultimately, the integration of gene expression and biochemical methods with sequence- and systems-based bioinformatics approaches will reveal profound insights regarding the importance of target contextual features in determining miRNA target recognition and regulatory outcome, as well as the importance of RNA interaction networks in enabling miRNA to regulate different target genes and functions in specific biological contexts. There is therefore a demand for the elegant design of future experiments such that principles of context-specific miRNA target recognition and regulatory outcome can be accurately modeled in normal developmental and disease states.
近年来,microRNA(miRNA)已成为包括细胞分化、增殖、凋亡以及突触可塑性等基本生物学过程的主要调控因子。然而,miRNA 与靶标结合的互补性只有部分匹配,因此很难确定 miRNA 在特定生物环境中的具体作用方式。本文综述了 miRNA 靶标识别和功能的关键原理,这些原理是通过生物学和生物信息学方法的逐步发展而得出的。最终,将基因表达和生化方法与基于序列和系统的生物信息学方法相结合,将揭示靶标上下文特征在决定 miRNA 靶标识别和调控结果中的重要性,以及 RNA 相互作用网络在使 miRNA 能够在特定生物环境中调节不同靶标基因和功能方面的重要性。因此,需要精心设计未来的实验,以便能够在正常发育和疾病状态下准确模拟特定 miRNA 靶标识别和调控结果的原理。