Z型核酸的形成及生物学功能研究进展  

Advances in Formation and Biological Function of Z-Form Nucleic Acids

作　　者：梁兴国[1,2] 刘梦琴 安然 张亚萍[4] Liang Xingguo;Liu Mengqin;An Ran;Zhang Yaping(State Key Laboratory of Marine Food Processing and Safety Control,College of Food Science and Engineering,Ocean University of China,Qingdao 266404,China;Laboratory for Marine Drugs and Bioproducts,Qingdao Marine Science and Technology Center,Qingdao 266237,China;School of Medicine and Pharmacy,Ocean University of China,Qingdao 266003,China;Shenzhen Bay Laboratory,Pingshan Translational Medicine Center,Shenzhen 518118,China)

机构地区：[1]中国海洋大学食品科学与工程学院,海洋食品加工与安全控制全国重点实验室,山东青岛266404 [2]青岛海洋科技中心海洋药物与生物制品功能实验室,山东青岛266237 [3]中国海洋大学医药学院,山东青岛266003 [4]坪山生物医药研发转化中心深圳湾实验室,广东深圳518118

出　　处：《中国海洋大学学报（自然科学版）》2024年第10期113-133,共21页Periodical of Ocean University of China

基　　金：国家自然科学基金青年科学基金项目(32102064);国家重点研究发展计划项目(2019YFC1604603);青岛市自然科学基金项目(24-4-4-zrjj-147-jch)资助。

摘　　要：近年来,具有左旋双螺旋结构的Z型核酸(包括Z-DNA和Z-RNA)的重要生物学功能不断被发现,但Z型核酸(ZNA)在体内的形成及发挥功能的机制仍然不清楚。一般Z型核酸本身并不能稳定存在,易转化为右旋双螺旋结构,需要通过与其特异性结合蛋白(如人体中的ZBP1和ADAR1)结合而稳定下来并发挥其功能。其具体功能包括,参与基因调控以维持机体健康(如抑制癌细胞转移、抑制氧化性组织损伤等),上调Z型核酸结合蛋白的表达以引起细胞坏死或炎症(如病毒感染、诱发自身免疫疾病等)。同时,由于Z型核酸难以研究,虽早在1979年得到确认,但到2015年前后一直发展缓慢;可喜的是,随着各种新的研究手段的出现,近年其研究发展迅速。本文主要综述了2017年以来的Z型核酸的生物学功能、形成机制、制备方法和检测方法等相关研究,具体内容包括Z型核酸介导的免疫反应、体内Z型核酸形成机制、利用拓扑限制形成稳定Z型核酸、体内外检测Z型核酸的方法等。显然,Z型核酸的形成及特性研究将拓展生物医药及纳米材料等领域的研究,Z型核酸将得到越来越多的应用。Recently,the important biological functions of Z-form nucleic acids(including Z-DNA and Z-RNA)with left-handed double helix have been discovered,but the mechanism of formation and function of Z-form nucleic acids in vivo is still unclear.Generally,Z-form nucleic acid is instable,and transforms to right-handed structure easily.Z-form needs to be stabilized and perform function by binding to specific binding proteins(such as ZBP1 and ADAR1 in human).The specific functions include participating in gene regulation to maintain health(such as inhibiting cancer cell metastasis,inhibiting oxidative tissue damage)and up-regulating the expression of Z-DNA binding proteins to cause necroptosis and inflammation(such as viral infection,inducing autoimmune diseases).However,the studies on Z-form nucleic acids were very difficult and slow from 1979 to 2015.Fortunately,with the development of various new research methods,the study of Z-form nucleic acids has become rapid in recent years.In this review,we summarize the research on function,formation mechanism,preparation method and detection method of Z-form nucleic acids published since 2017,including the immunoreaction mediated by Z-form nucleic acids,Z-form formation mechanism in vivo,the detailed mechanism of binding to related proteins,topologically constrained formation of stable Z-form nucleic acid,the methods for detecting Z-form,and so on.Obviously,the study on formation and characterization of Z-form nucleic acids will expand the fields of biomedicine and nanomaterials,so that Z-form nucleic acids have more and more significant applications.

关 键 词：Z-DNA Z-RNA 核酸结构 拓扑限制 B-Z转变 

分 类 号：Q71[生物学—分子生物学]