Green D, Dalmay T, Chapman T
Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, UK.
School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich, UK.
Heredity (Edinb). 2016 Feb;116(2):125-34. doi: 10.1038/hdy.2015.84. Epub 2015 Sep 30.
The regulation of gene expression is of fundamental importance to maintain organismal function and integrity and requires a multifaceted and highly ordered sequence of events. The cyclic nature of gene expression is known as 'transcription dynamics'. Disruption or perturbation of these dynamics can result in significant fitness costs arising from genome instability, accelerated ageing and disease. We review recent research that supports the idea that an important new role for small RNAs, particularly microRNAs (miRNAs), is in protecting the genome against short-term transcriptional fluctuations, in a process we term 'microguarding'. An additional emerging role for miRNAs is as 'micromessengers'-through alteration of gene expression in target cells to which they are trafficked within microvesicles. We describe the scant but emerging evidence that miRNAs can be moved between different cells, individuals and even species, to exert biologically significant responses. With these two new roles, miRNAs have the potential to protect against deleterious gene expression variation from perturbation and to themselves perturb the expression of genes in target cells. These interactions between cells will frequently be subject to conflicts of interest when they occur between unrelated cells that lack a coincidence of fitness interests. Hence, there is the potential for miRNAs to represent both a means to resolve conflicts of interest, as well as instigate them. We conclude by exploring this conflict hypothesis, by describing some of the initial evidence consistent with it and proposing new ideas for future research into this exciting topic.
基因表达的调控对于维持机体功能和完整性至关重要，且需要一系列多方面且高度有序的事件。基因表达的循环特性被称为“转录动力学”。这些动力学的破坏或扰动会导致因基因组不稳定、加速衰老和疾病而产生重大的适应性代价。我们回顾了最近的研究，这些研究支持以下观点：小RNA，特别是微小RNA（miRNA），在保护基因组免受短期转录波动影响的过程中发挥着重要的新作用，我们将这一过程称为“微保护”。miRNA的另一个新出现的作用是作为“微信使”——通过改变它们在微泡中运输到的靶细胞中的基因表达来发挥作用。我们描述了稀少但正在出现的证据，即miRNA可以在不同细胞、个体甚至物种之间移动，以产生生物学上显著的反应。有了这两个新作用，miRNA有潜力保护机体免受有害基因表达变化的干扰，并自身干扰靶细胞中的基因表达。当这些细胞间的相互作用发生在缺乏适应性利益一致性的不相关细胞之间时，它们经常会面临利益冲突。因此，miRNA有可能既是解决利益冲突的一种手段，也是引发利益冲突的因素。我们通过探讨这一冲突假说、描述一些与之相符的初步证据，并为这一令人兴奋的主题的未来研究提出新想法来进行总结。
