2015.2.9,单革教授实验室在Nature Structural & Molecular Biology发表article,报导了其实验室发现的一类新型非编码RNA以及此类非编码RNA的功能和功能机理。
非编码RNA是一大类不编码蛋白质、而在细胞中起着调控作用的RNA分子。单革教授实验室发现了一类新型的环状非编码RNA,在这类环状RNA中,内含子没有被除去、而是被保留在环形RNA当中,因此这类RNA被作者命名为外显子-内含子环形RNA(EIciRNA)。该文研究了外显子-内含子环形RNA的功能,发现此类非编码RNA可以调控其自身所在的基因的表达。进一步的研究表明外显子-内含子环形RNA是通过招募U1小RNA蛋白复合物(U1 snRNP)来促进基因转录的起始。
环形RNA分子是最近数年才引起研究人员注意的,而此前的研究主要集中在线形RNA分子上。在此研究之前、报导的已知环形RNA分子都是由外显子构成的、其中并不包含内含子序列。研究发现,外显子-内含子环形RNA几乎完全定位于细胞核中,这一点也与以前发现的其它完全由外显子形成的环形RNA的细胞质定位不同。在此文当中作者对为什么这些RNA会成为环形而不是线形分子也进行了研究,发现成环序列两端经常会有互补的重复序列存在。此次发现外显子-内含子环形RNA、以及对其功能和功能机理的研究,加深了对非编码RNA种类和功能的认识。
文章的共同第一作者为李兆勇副教授以及博士生黄川和包纯。研究得到了科技部、中科院、国家基金委、以及中科大非编码RNA功能及功能机理创新团队的经费支持。
Zhaoyong Li*, Chuan Huang*, Chun Bao*, Liang Chen, Mei Lin, Xiaolin Wang, Guolin Zhong, Bin Yu, Wanchen Hu, Limin Dai, Pengfei Zhu, Zhaoxia Chang, Qingfa Wu, Yi Zhao, Ya Jia, Ping Xu, Huijie Liu, Ge Shan. Exon-Intron circular RNAs regulate transcription in the nucleus. Nat. Struct. Mol. Bio. 2015, 22: 2959.
Abstract
Noncoding RNAs (ncRNAs) play numerous roles in development and disease, and one of the prominent roles of ncRNAs is to regulate gene expression. A vast number of circular RNAs (circRNAs) were identified, and some were shown to function as microRNA sponges in animal cells. Here, we report a class of circRNAs associated with RNA polymerase II in human cells. In these circRNAs, exons are circularized with introns “retained” between exons, which we term exon-intron circRNAs or EIciRNAs. EIciRNAs predominantly localize in the nucleus, interact with U1 snRNP, and promote the transcription of their parent genes. These findings reveal a novel role for circRNAs in regulating gene expression in the nucleus, suggesting that EIciRNAs enhance the expression of their parent genes in cis and highlight a regulatory strategy for transcriptional control via specific RNA-RNA interaction between U1 snRNA and EIciRNAs.
附论文链接:http://www.nature.com/nsmb/journal/vaop/ncurrent/full/nsmb.2959.html