Wang Yuru, Zheng Yuxuan, Beal Peter A
University of California, Davis, CA, United States.
University of California, Davis, CA, United States.
Enzymes. 2017;41:215-268. doi: 10.1016/bs.enz.2017.03.006. Epub 2017 Apr 14.
Inosine is one of the most common modifications found in human RNAs and the Adenosine Deaminases that act on RNA (ADARs) are the main enzymes responsible for its production. ADARs were first discovered in the 1980s and since then our understanding of ADARs has advanced tremendously. For instance, it is now known that defective ADAR function can cause human diseases. Furthermore, recently solved crystal structures of the human ADAR2 deaminase bound to RNA have provided insights regarding the catalytic and substrate recognition mechanisms. In this chapter, we describe the occurrence of inosine in human RNAs and the newest perspective on the ADAR family of enzymes, including their substrate recognition, catalytic mechanism, regulation as well as the consequences of A-to-I editing, and their relation to human diseases.
肌苷是人类RNA中最常见的修饰之一,作用于RNA的腺苷脱氨酶(ADARs)是负责其产生的主要酶。ADARs于20世纪80年代首次被发现,从那时起,我们对ADARs的理解有了巨大的进展。例如,现在已知ADAR功能缺陷会导致人类疾病。此外,最近解析的与RNA结合的人类ADAR2脱氨酶的晶体结构,为催化和底物识别机制提供了见解。在本章中,我们描述了肌苷在人类RNA中的存在情况,以及关于ADAR酶家族的最新观点,包括它们的底物识别、催化机制、调控以及A到I编辑的后果,以及它们与人类疾病的关系。