Cancer Institute, Xuzhou Medical University, 84 West Huaihai Road, Xuzhou, 221002, Jiangsu Province, China.
Center of Clinical Oncology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
Mol Cancer. 2022 Jan 7;21(1):13. doi: 10.1186/s12943-021-01484-7.
Circular RNAs (circRNAs) are classified as noncoding RNAs because they are devoid of a 5' end cap and a 3' end poly (A) tail necessary for cap-dependent translation. However, increasing numbers of translated circRNAs identified through high-throughput RNA sequencing overlapping with polysome profiling indicate that this rule is being broken. CircRNAs can be translated in cap-independent mechanism, including IRES (internal ribosome entry site)-initiated pattern, MIRES (mA internal ribosome entry site) -initiated patterns, and rolling translation mechanism (RCA). CircRNA-encoded proteins harbour diverse functions similar to or different from host proteins. In addition, they are linked to the modulation of human disease including carcinomas and noncarcinomas. CircRNA-related translatomics and proteomics have attracted increasing attention. This review discusses the progress and exclusive characteristics of circRNA translation and highlights the latest mechanisms and regulation of circRNA translatomics. Furthermore, we summarize the extensive functions and mechanisms of circRNA-derived proteins in human diseases, which contribute to a better understanding of intricate noncanonical circRNA translatomics and proteomics and their therapeutic potential in human diseases.
环状 RNA（circRNAs）被归类为非编码 RNA，因为它们缺乏 5'端帽子和 3'端 poly(A)尾，而这些结构对于帽子依赖性翻译是必需的。然而，通过高通量 RNA 测序与多核糖体谱分析重叠鉴定出越来越多的被翻译的 circRNAs，表明这个规则正在被打破。circRNAs 可以通过非帽子依赖机制进行翻译，包括 IRES（内部核糖体进入位点）起始模式、MIRES（mA 内部核糖体进入位点）起始模式和滚动翻译机制（RCA）。circRNA 编码的蛋白质具有与宿主蛋白相似或不同的多种功能。此外，它们与包括癌和非癌在内的人类疾病的调节有关。circRNA 相关的转译组学和蛋白质组学引起了越来越多的关注。本文讨论了 circRNA 翻译的进展和独特特征，并强调了最新的 circRNA 转译组学的机制和调节。此外，我们总结了 circRNA 衍生蛋白在人类疾病中的广泛功能和机制，这有助于更好地理解复杂的非规范 circRNA 转译组学和蛋白质组学及其在人类疾病中的治疗潜力。
