增强子RNA的功能特性及其在人类疾病中的重要调控作用

Functional Properties of Enhancer RNA and Its Important Regulatory Roles in Human Diseases

增强子是基因组上一段可以被转录调控蛋白识别并结合的区域,作为顺式调控元件和启动子共同参与基因转录过程。增强子在激活状态下,打开局部染色质并暴露DNA基序以吸引转录因子,从而进一步招募RNA聚合酶产生一类非编码RNA,即增强子RNA(enhancer RNA,eRNA)。eRNA可促进增强子与启动子特异性染色质远程互作参与基因转录调节,或与转录因子等调控蛋白结合促进基因转录,具有多样的功能和调控机制,从而在细胞的发育和分化、疾病发生发展等众多生物过程中起重要作用。该文就e RNA特性、功能、鉴定、数据库资源,以及eRNA在人类神经系统疾病、癌症、免疫代谢类疾病、心血管疾病等中的功能作用研究进展作一系统综述,探讨eRNA的未来研究方向,及在疾病中作为潜在治疗靶点的可能及目前存在的挑战。

Enhancer is a region of the genome that can recognize and bind to transcriptional regulatory proteins,and is involved in the gene transcription process as a cis-regulatory element together with promoter.Enhancers,in their activated state,open local chromatin and expose DNA mores to attract transcription factors,thereby further recruiting RNA polymerase to produce a class of non-coding RNA—eRNA(enhancer RNA).eRNA can promote the remote interaction between enhancer and promoter-specific chromatin to participate in gene transcription regulation,or combine with regulatory proteins such as transcription factors to promote gene transcription.eRNA has a variety of functions and regulatory mechanisms,and thus plays important roles in many biological processes such as cell development and differentiation and disease development.In this paper,the characteristics,function,identification and database resources of eRNA,as well as the functional role of eRNA in human neurological diseases,cancers,immune metabolism diseases and cardiovascular diseases are systematically reviewed,and the future research direction of eRNA,as well as the possibility as potential thera-peutic targets in diseases and the existing challenges are discussed.