Cell:陈玲玲全面综述circRNA的表征、功能及应用

2022-05-22 生物世界 生物世界

近年来,也有研究表明一部分环形RNA能够作为翻译模版编码功能性小肽,从而调控热休克应激、肿瘤细胞迁移侵袭等生物学过程。

2022年5月17日,中国科学院分子细胞科学卓越创新中心陈玲玲团队受邀在国际顶尖学术期刊 Cell 在线发表了题为:Circular RNAs: characterization, cellular roles and applications 的综述论文。

该论文系统梳理了针对环形RNA研究的生物学技术手段,总结了其以非编码RNA形式参与调控细胞内基因表达和通过编码功能性小肽调控相关生物学过程的最新研究成果,并展望了环形RNA在生物医学领域的应用前景。

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区别于传统认识,许多体内稳定存在的长非编码 RNA 以共价闭合环形结构存在,其中大部分由反向剪接产生,被称为环形RNA(circular RNA, circRNA)。近年来,随着转录组测序新技术的发展和应用,以及相应计算生物学分析流程的不断优化,科学家在真核生物中发现了多达数十万条的外显子反向剪接环形RNA。

陈玲玲团队这篇最新发表环形RNA特邀综述论文中,系统性地总结和梳理了近年来国际上环形RNA的生物学功能及调控机制等研究成果。环形RNA的生成加工在多个水平受到严格调控,其出核及降解机制也与同源线性mRNA不同,该综述从发现、鉴定和研究环形RNA的生物学手段出发(图A),总结了环形RNA以非编码RNA的形式如:miRNA和蛋白质的分子海绵、影响转录、干扰mRNA前体的正常剪接、调控mRNA分子翻译、形成环形RNA蛋白质复合体、与mRNA竞争性结合蛋白质等机制,参与免疫、代谢、神经系统发育和细胞增殖等生物学过程中(图B)。

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图A:环形RNA的发现、鉴定和功能解析手段

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图B:环形RNA参与调控细胞内多种生物学过程的分子模型

近年来,也有研究表明一部分环形RNA能够作为翻译模版编码功能性小肽,从而调控热休克应激、肿瘤细胞迁移侵袭等生物学过程(图C)。值得一提的是,环形RNA的稳定性和特殊的免疫原性,使得环形RNA具有很好的转化应用场景。该论文总结了环形RNA一系列转化应用场景:如作为RNA适配体、miRNA和蛋白质的分子海绵、反义RNA、调控细胞内天然免疫反应、蛋白质翻译载体及疾病相关分子标志物等,为进一步改造和利用环形RNA提供新思路(图D)。

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图C:可翻译的环形RNA及其调控模型

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图D:环形RNA在生物医学领域的转化应用场景

分子细胞卓越中心副研究员刘楚霄为该论文的第一作者,陈玲玲研究员为该论文的通讯作者。该项工作得到了来自科技部、中科院和基金委的经费支持。

论文链接:

https://www.cell.com/cell/fulltext/S0092-8674(22)00468-8

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    2022-09-24 维他命
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    2022-05-22 病毒猎手

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