Salmanidis Marika, Pillman Katherine, Goodall Gregory, Bracken Cameron
Centre for Cancer Biology, University of South Australia, Adelaide, Australia.
Centre for Cancer Biology, University of South Australia, Adelaide, Australia; Discipline of Medicine, University of Adelaide, Adelaide, Australia; School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia.
Int J Biochem Cell Biol. 2014 Sep;54:304-11. doi: 10.1016/j.biocel.2014.03.010. Epub 2014 Mar 25.
The function of microRNAs is well characterized in the cytoplasm, where they direct an Argonaute-containing complex to target and repress mRNAs. More recently, regulatory roles for microRNAs and Argonaute have also been reported in the nucleus where microRNAs guide Argonaute to target gene promoters and directly regulate transcription in either a positive or a negative manner. Deep sequencing has revealed a high abundance of endogenous microRNAs within the nucleus, and in silico target prediction suggests thousands of potential microRNA:promoter interaction sites. The predicted high frequency of miRNA:promoter interactions is supported by chromatin immunoprecipitation, indicating the microRNA-dependent recruitment of Argonaute to thousands of transcriptional start sites and the subsequent regulation of RNA polymerase-II occupancy and chromatin modifiers. In this review we discuss the evidence for, and mechanisms associated with, direct transcriptional regulation by microRNAs which may represent a significant and largely unexplored aspect of microRNA function. This article is part of a Directed Issue entitled: The non-coding RNA revolution.
微小RNA的功能在细胞质中已得到充分表征，在那里它们引导含AGO蛋白的复合物靶向并抑制信使核糖核酸。最近，微小RNA和AGO蛋白在细胞核中的调控作用也有报道，微小RNA在细胞核中引导AGO蛋白靶向基因启动子，并以正向或负向方式直接调控转录。深度测序揭示了细胞核内大量的内源性微小RNA，计算机模拟靶点预测表明有成千上万潜在的微小RNA：启动子相互作用位点。染色质免疫沉淀支持了预测的微小RNA：启动子相互作用的高频率，表明微小RNA依赖的AGO蛋白募集到数千个转录起始位点，以及随后对RNA聚合酶II占位和染色质修饰剂的调控。在这篇综述中，我们讨论了微小RNA直接转录调控的证据及其相关机制，这可能代表了微小RNA功能中一个重要且很大程度上未被探索的方面。本文是名为：非编码RNA革命的定向问题的一部分。
