Ningbo University School of Medicine, Ningbo, China.
Li Huili Hospital Affiliated to Ningbo University School, Ningbo, China.
J Clin Lab Anal. 2021 Jul;35(7):e23866. doi: 10.1002/jcla.23866. Epub 2021 Jun 7.
Circular RNAs (circRNAs) constitute a class of covalently closed RNA molecules. With the continuous advancement of high-throughput sequencing technology and bioinformatics tools, many circRNAs have been identified in various human tissues and cell lines. Notably, recent studies have indicated that some circRNAs have translational functions. Internal ribosome entry sites and the N6-methyladenosine modification mediate cap-independent translation. This review describes these two translation mechanisms and verification methods at the molecular level. Databases (including ORF Finder, Pfam, BLASTp, CircRNADb, CircBase, CircPro, CircCode, IRESite, IRESbase) were used to analyze whether circRNAs have the structural characteristic of translation. CircRNA minigene reporter system containing green fluorescent protein (GFP) confirmed the translation potential of circRNAs. Also, we briefly summarize the roles of proteins/peptides encoded by circRNAs (circFBXW7, circFNDC3B, circLgr4, circPPP1R12A, circMAPK1, circβ-catenin, circGprc5a, circ-SHPRH, circPINTexon2, circAKT3) that have been verified thus far in human cancers (triple-negative breast cancer, colon cancer, gastric cancer, hepatocellular carcinoma, bladder cancer, glioblastoma). Those findings suggest circRNAs have a great implication in translation of the human genome.
环状 RNA（circRNA）是一类共价闭合的 RNA 分子。随着高通量测序技术和生物信息学工具的不断进步，在各种人类组织和细胞系中已经鉴定出许多 circRNA。值得注意的是，最近的研究表明，一些 circRNA 具有翻译功能。内部核糖体进入位点和 N6-甲基腺苷修饰介导无帽依赖性翻译。本文描述了这两种在分子水平上的翻译机制和验证方法。数据库（包括 ORF Finder、Pfam、BLASTp、CircRNADb、CircBase、CircPro、CircCode、IRESite、IRESbase）用于分析 circRNA 是否具有翻译的结构特征。含有绿色荧光蛋白（GFP）的 circRNA 迷你基因报告系统证实了 circRNA 的翻译潜力。此外，我们还简要总结了迄今为止在人类癌症（三阴性乳腺癌、结肠癌、胃癌、肝细胞癌、膀胱癌、胶质母细胞瘤）中已验证的由 circRNA 编码的蛋白质/肽（circFBXW7、circFNDC3B、circLgr4、circPPP1R12A、circMAPK1、circβ-catenin、circGprc5a、circ-SHPRH、circPINTexon2、circAKT3）的作用。这些发现表明 circRNA 在人类基因组的翻译中具有重要意义。
