m^(6)A甲基化在病毒感染中的作用研究进展

The role of m^(6)A methylation in virus infection

RNA分子上存在着多种修饰方式,如5-甲基胞嘧啶(m 5C)、6-甲基腺嘌呤(m^(6)A)、1-甲基腺嘌呤(m 1A)和假尿嘧啶(Ψ)等。而其中RNA分子腺嘌呤第6位氮原子上发生的甲基化修饰,即m^(6)A(N 6-methyladenosine)是一种非常重要的表观遗传修饰方式,在干细胞命运决定、肌肉发育、精子形成以及肿瘤发生中都起着重要的作用。在40多年前已经发现病毒RNA中含有m^(6)A修饰,m^(6)A功能的行使主要在甲基转移酶(编码器“Writers”)、去甲基化酶(消码器“Erasers”)和结合蛋白(读码器“Readers”)的参与下进行,他们共同调控m^(6)A的发生。不同种类的病毒,在不同的细胞和组织中产生不同的m^(6)A修饰。而m^(6)A修饰对病毒和宿主RNA的调控机制不尽相同。m^(6)A修饰对宿主的影响在一定程度上与宿主的免疫系统有关。MeRIP-Northern blot和MeRIP-seq等技术的发展帮助加深对该领域的研究。本文综述了m^(6)A甲基化在甲型流感病毒(influenza A virus,IAV)、人类免疫缺陷病毒1型(Human immunodeficiency virus 1,HIV-1)、猴空泡病毒(Simian vacuolating virus 40/Simian virus 40,SV40)、卡波西氏肉瘤相关疱疹病毒(Kaposi’s sarcoma-associated herpesvirus,KSHV)、丙型肝炎病毒(Hepatitis C virus,HCV)、乙型肝炎病毒(Hepatitis B virus,HBV)、肠道病毒71型(Enterovirus 71,EV71)、呼吸道合胞病毒(Rous sarcoma virus,RSV)和植物病毒感染中的作用,探讨该甲基化修饰在病毒与宿主相互作用中扮演的重要角色。

It is well known that there are many kinds of modifications on RNA,such as 5-methylcytosine(m 5C),6-methyladenine(m^(6)A),1-methyladenine(m 1A)and pseudouracil(ψ).Among them,m^(6)A(N 6-methyladenosine)is a very important epigenetic modification,which plays an important role in the fate determination of stem cells,muscle development,sperm formation and tumorigenesis.It has been more than 40 years since m^(6)A modification was discovered in viral RNA.The function of m^(6)A modification is regulated by methyltransferase(“Writers”),demethylase(“Erasers”)and binding protein(“Readers”).These three kinds of enzyme regulate the modification of m^(6)A together.On the one hand,the m^(6)A modifications in different types of viruses differ,depending on the types of cells and tissues.m^(6)A modification has different regulatory mechanisms on virus and host RNA respectively.On the other hand,the influence of m^(6)A modification on host is related to the host’s immune system to a certain extent.The development of MeRIP-Northern Blot and MeRIP-seq technologies helps deepen researches in this field.This article mainly focuses on the role of m^(6)A modification in the infection of influenza A virus(IAV),Human immune deficiency virus 1(HIV-1),Simian vacuolating virus 40/Simian virus 40(SV40),Kaposi’s sarcoma-associated herpesvirus(KSHV),Hepatitis C virus(HCV),Hepatitis B virus(HBV),Enterovirus 71(EV71),Rous sarcoma virus(RSV)and plant virus,and explores the important role that this methylation modification plays in the interaction between the virus and the host.