Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Cancer Lett. 2017 Dec 28;411:27-34. doi: 10.1016/j.canlet.2017.09.036. Epub 2017 Sep 30.
Adenosine deaminases acting on RNA (ADARs) are enzymes that catalyze the conversion of adenosine (A) to inosine (I) in double-stranded RNAs. Inosine exhibits similar properties as guanosine. As a result, A-to-I editing has a great impact on edited RNAs, not only affecting the base pairing properties, but also altering codons after translation. A-to-I editing are known to mediate and diversify transcripts. However, the overall biological effect of ADARs are still largely unknown. Aberrant ADAR activity and editing dysregulation are present in a variety of cancers, including hepatocellular carcinoma, chronic myelogenous leukemia, glioblastoma and melanoma. ADAR-mediated A-to-I editing can influence uncontrolled nucleotide changes, resulting in susceptibility of cells to developmental defects and potential carcinogenicity. A deeper understanding of the biological function of ADARs may provide mechanistic insights in the development of new cancer therapy. Here, we discuss recent advances in research on ADAR in detail including the structure and function of ADARs, the biochemistry of ADAR-mediated RNA editing, and the relevance of ADAR proteins in cancer.
腺嘌呤脱氨酶作用于 RNA（ADARs）是一种能够催化双链 RNA 中腺嘌呤（A）向肌苷（I）转化的酶。肌苷的性质与鸟嘌呤类似。因此，A 到 I 的编辑对编辑后的 RNA 有很大的影响，不仅影响碱基配对的性质，而且还改变翻译后的密码子。A 到 I 的编辑被认为是介导和多样化转录本的过程。然而，ADAR 的整体生物学效应在很大程度上仍然未知。异常的 ADAR 活性和编辑失调存在于多种癌症中，包括肝细胞癌、慢性髓性白血病、神经胶质瘤和黑色素瘤。ADAR 介导的 A 到 I 的编辑可以影响不受控制的核苷酸变化，导致细胞易发生发育缺陷和潜在的致癌性。深入了解 ADAR 的生物学功能可能为开发新的癌症治疗方法提供机制上的见解。在这里，我们详细讨论了 ADAR 研究的最新进展，包括 ADAR 的结构和功能、ADAR 介导的 RNA 编辑的生物化学以及 ADAR 蛋白在癌症中的相关性。
