环状RNA翻译能力研究进展

doi:10.16288/j.yczz.19-354

遗传 ›› 2020, Vol. 42 ›› Issue (5): 423-434.doi: 10.16288/j.yczz.19-354

• 综述 • 下一篇

环状RNA翻译能力研究进展

郑帅龙, 李利(), 张红平()

四川农业大学动物遗传育种研究所,成都 611130

收稿日期:2020-01-07 修回日期:2020-03-24 出版日期:2020-05-20 发布日期:2020-04-01
通讯作者: 李利,张红平 E-mail:lily@sicau.edu.cn;zhp@sicau.edu.cn
基金资助:
国家自然科学基金项目编号(31772578);国家自然科学基金项目编号(31672402);四川省科技支撑计划项目资助编号(2016NYZ0045)

Progress on translation ability of circular RNA

Shuailong Zheng, Li Li(), Hongping Zhang()

Institute of Animal Genetics and Breeding, Sichuan Agricultural University, Chengdu 611130, China

Received:2020-01-07 Revised:2020-03-24 Online:2020-05-20 Published:2020-04-01
Contact: Li Li,Zhang Hongping E-mail:lily@sicau.edu.cn;zhp@sicau.edu.cn
Supported by:
Supported by the National Natural Science Foundation of China Nos(31772578);Supported by the National Natural Science Foundation of China Nos(31672402);the Science and Technology Program of Sichuan Province No(2016NYZ0045)

摘要/Abstract

摘要：

随着高通量测序技术和翻译组学研究的快速发展,对环状RNA (circular RNA, circRNA)翻译能力的研究日益成为热点。已有研究表明,circRNA自身可以翻译为蛋白,其蛋白功能与人类疾病发生发展有着密切联系,而且其有望成为mRNA的理想替代品,未来可被广泛地应用在蛋白质工程。本文系统综述了circRNA来源、形成方式和主要特征、翻译蛋白的方式、翻译能力的鉴定和功能验证,归纳了近年来circRNA翻译在人类疾病中的研究进展及其在蛋白质工程的应用,并对后续研究关注的问题进行了展望,以期为相关领域的研究提供参考。

关键词: 环状RNA, 蛋白翻译, 鉴定方法

Abstract:

With the rapid development of high-throughput sequencing technology and translatome studies, the translational ability of circular RNA (circRNA) has gradually attracted much attention. Previous studies have shown that circRNA itself can be translated into proteins, whose function is closely related to the occurrence and development of human diseases. And it is expected to become an ideal substitute for mRNA, which can be widely used in protein engineering in the future. In this review, we systematically summarize the sources, biogenesis and features of circRNA, the driving models of circRNA translation, identification and functional verification of circRNA translation. We also sum up the latest research progress of circRNA translation in human diseases and its application in protein engineering, and make prospective anticipations for future research directions, which may offer more theoretical references for related researches in this field.

Key words: circular RNA, protein translation, identification methods

郑帅龙, 李利, 张红平. 环状RNA翻译能力研究进展[J]. 遗传, 2020, 42(5): 423-434.

Shuailong Zheng, Li Li, Hongping Zhang. Progress on translation ability of circular RNA[J]. Hereditas(Beijing), 2020, 42(5): 423-434.

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名称	工具介绍	参考文献
ORFfinder	一个图形序列分析工具,可以分析并检索出circRNA序列中所有潜在的ORF	[39]
CPC2	通过输入circRNA序列,可预测其编码能力	[40]
CPAT	通过对circRNA序列信息进行分析,评估其编码潜力	[41]
IRESfinder	基于k-mer特征识别真核细胞中RNA序列上的IRES	[42]
IRESite	基于已有68个病毒和115个真核细胞的实验数据,收录了大量的具有IRES位点的基因, 可对circRNA序列进行比对,预测circRNA上潜在的IRES位点	[43]
Sramp	对哺乳动物的circRNA序列进行检索,寻找m⁶A 基序	[44]
m⁶Apred	对酿酒酵母中m⁶A基序进行预测	[45]
Pfam 32.0	通过预测circRNA翻译产物的潜在结构域,进而预测其功能	[46]
CircCode	基于RNA-seq或者Ribo-seq (核糖体印记与深度测序)数据,筛选结合有核糖体的circRNA	[47]

名称	数据库介绍	参考文献
circRNAdb	收集了32,914条人类外显子circRNA记录,是首个汇总可编码蛋白的circRNA的数据库	[48]
circBank	收录了140,790条人类circRNA的记录,是目前关于人类已知circRNA最全的数据库	[49]
circBase	收集了包括人、小鼠、秀丽线虫(Caenorhabditis elegans)等共6个物种的circRNA信息,是目前涵盖物种数目最多的circRNA数据库	[50]
CSCD	肿瘤特异性circRNA数据库,可以对circRNA的RBP、ORF、亚细胞定位和可变剪切进行预测	[51]
TSCD	circRNA组织特异性表达分析数据库,收录了人和小鼠的circRNA信息	[52]
CIRCpedia V2	收录6个不同物种的180多个RNA-seq数据和26万个circRNA注释,可对人类和小鼠间circRNA进行保守分析	[53]
CircInteractome	通过预测circRNA是否含有已被验证过的IRES,判断其是否具有潜在的翻译能力	[54]
CircNet	对人类464个样本的RNA-seq数据系统地整理挖掘后建立的数据库,它提供了新circRNA的鉴定、circRNA-miRNA-mRNA的互作网络、circRNA亚型的表达水平、circRNA亚型的基因组注释和circRNA亚型的序列等信息	[55]
plantcircbase	植物circRNA的综合数据库,包含了拟南芥(Arabidopsis thaliana)、水稻(Oryza sativa)、玉米(Zea mays)、番茄(Solanum lycopersicum)和大麦(Hordeum vulgare)等物种的circRNA信息,可以使circRNA结构可视化	[56]
Circ2Traits	收录了与疾病和性状潜在相关的circRNA信息	[57]
circAtlas	收录了包括人、猕猴(Macaca mulatta)、小鼠、褐家鼠(Rattus norvegicus)、野猪(Sus scrofa)和鸡(Gallus domesticus)等物种的circRNA序列信息,可对不同物种间circRNA保守性进行分析	[58]

方法	原理	用途	参考文献
核糖体印记与深度测序技术	被核糖体包裹的RNA片段不易被RNase降解,回收片段测序得到与核糖体结合的序列信息	筛选出结合有核糖体的circRNA	[59,60]
免疫组化反应	利用抗原与相应的抗体进行免疫反应后,通过相应的显色反应,以检测相应的目的蛋白的表达	检测circRNA生成的蛋白, 进行定性、定量和定位	[61]
Western Blot	设计特异性抗体与抗原进行免疫反应后,通过相应的显色反应,以检测相应的目的蛋白的表达	检测circRNA生成的蛋白,进行定性和定量	[12]
免疫沉淀	利用抗体特异性反应纯化富集目的蛋白	纯化富集目的蛋白	[61]
质谱检测	质谱分析是先将物质离子化,按离子的质荷比分离,然后测量各种离子谱峰的强度而实现分析目的的一种分析方法	检测circRNA新生成的蛋白,获得蛋白序列信息	[61]
RNA结合蛋白免疫沉淀	运用针对目标蛋白的抗体把相应的RNA-蛋白复合物沉淀下来,经过分离纯化就可以对结合在复合物上的RNA进行q-PCR验证或者测序分析	验证circRNA与翻译起始相关蛋白或因子的相互作用	[62]
蛋白质体外结合实验	将RNA进行标记(如生物素探针标记),再与细胞裂解液共同孵育,从而形成RNA-蛋白质复合物,之后再分离复合物得到蛋白质,通过western blot或质谱检测检测蛋白质	验证circRNA与翻译起始相关蛋白或因子的相互作用	[63]

circRNA	蛋白	翻译蛋白方式	人类疾病	蛋白功能	参考文献
circZNF609	未知	IRES介导	杜氏型肌营养不良症	未知	[12]
circFBXW7	FBXW7-185aa	IRES介导	恶性胶质瘤	抑制	[14]
circE7	E7蛋白	m⁶A介导	宫颈癌	促进	[36]
circAKT3	AKT3-174aa	IRES介导	恶性胶质瘤	抑制	[61]
circPINT	PINT-87aa	IRES介导	恶性胶质瘤	抑制	[64]
circβ-catenin	β-catenin-370aa	IRES介导	肝癌	促进	[65]
circGprc5a	circGprc5a-peptide	未知	膀胱癌	促进	[66]
CDR1as、circANKH、 circASXL1、circCSNK1G3、 circKIAA1429和circSIPA1L1	未知	未知	扩张型心肌病	未知	[67]
circSHPRH	SHPRH-146aa	IRES介导	恶性胶质瘤	抑制	[68]

环状RNA翻译能力研究进展

Progress on translation ability of circular RNA

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