Zhang Yifan, Bryant Jack, Herron Laura, Mali Prashant
Department of Bioengineering, University of California, San Diego, CA, 92093, United States.
Nucleic Acids Res. 2025 Jul 8;53(13). doi: 10.1093/nar/gkaf672.
RNA processing is essential for proper cellular function, contributing to protein and cell state diversity, and is often dysregulated in diseased states. A key subset of RNA regulators is the double-stranded RNA-specific adenosine deaminase (ADAR) protein family, which hydrolytically deaminates double-stranded RNA, causing an adenosine-to-inosine edit (A-to-I). Active ubiquitously throughout the body, this pleiotropic protein family plays critical roles in embryonic patterning, neurological function, and immune regulation. Their aberrant activity has in turn been implicated in a spectrum of disorders, including cancer, metabolic diseases, and autoimmune conditions. By instead purposefully modulating their activity, ADARs have been leveraged to create a versatile toolset for transcriptome engineering. This includes enabling programmable RNA editing, controlled RNA splicing, reversibly modulating protein interactions, and altering cellular inflammation. Here, we review the pleiotropic functions and versatile applications of ADARs, as well as outline areas for growth and potential new avenues in both therapeutics and research.
RNA加工对于细胞的正常功能至关重要，有助于蛋白质和细胞状态的多样性，并且在疾病状态下常常失调。RNA调节因子的一个关键子集是双链RNA特异性腺苷脱氨酶（ADAR）蛋白家族，该家族对双链RNA进行水解脱氨，导致腺苷到肌苷的编辑（A到I）。这个多效性蛋白家族在全身普遍活跃，在胚胎发育模式、神经功能和免疫调节中发挥着关键作用。它们的异常活性反过来又与一系列疾病有关，包括癌症、代谢疾病和自身免疫性疾病。通过有目的地调节它们的活性，ADAR已被用于创建一个用于转录组工程的多功能工具集。这包括实现可编程的RNA编辑、可控的RNA剪接、可逆地调节蛋白质相互作用以及改变细胞炎症。在这里，我们综述了ADAR的多效性功能和多功能应用，并概述了治疗和研究中有待发展的领域以及潜在的新途径。
