Circular RNA, the Key for Translation.
Circular RNA, the Key for Translation.
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DOI：
10.3390/ijms21228591
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发表时间：
2020-11-14
影响因子：
5.6
通讯作者：
Lacazette E
中科院分区：
文献类型：
--
作者：
Prats AC;David F;Diallo LH;Roussel E;Tatin F;Garmy-Susini B;Lacazette E
直到20世纪90年代，人们才认为真核生物的翻译机器无法翻译环状RNA。然而，发现了内部核糖体进入位点（IRES）和m6 A诱导的核糖体接合位点（MIRES），促进了5′端非依赖性翻译起始。今天，一个新的所谓的“非编码”环状RNA（circRNA）家族已经出现，揭示了5′端独立翻译的关键作用。CircRNA通过其海绵功能对翻译控制具有强烈影响，并且当它们被翻译成具有病理生理作用的蛋白质时形成新的mRNA家族。虽然关于共价闭合的circRNA的翻译没有更多的疑问，但典型mRNA的线性仅是理论上的：三十多年来已经证明多聚核糖体表现出环状形式，并且mRNA功能性环化已经在20世纪90年代通过起始因子eIF 4G与poly（A）结合蛋白的相互作用得到证实。最近，已经报道了3′-5′相互作用的其他机制，包括m6 A修饰。功能性环化通过核糖体再循环和加速翻译起始速率来增强翻译。共价和非共价闭合环状mRNA翻译景观的更新表明，环状RNA可能是翻译的规则，对疾病发展和生物技术应用有重要影响。
It was thought until the 1990s that the eukaryotic translation machinery was unable to translate a circular RNA. However internal ribosome entry sites (IRESs) and m6A-induced ribosome engagement sites (MIRESs) were discovered, promoting 5′ end-independent translation initiation. Today a new family of so-called “noncoding” circular RNAs (circRNAs) has emerged, revealing the pivotal role of 5′ end-independent translation. CircRNAs have a strong impact on translational control via their sponge function, and form a new mRNA family as they are translated into proteins with pathophysiological roles. While there is no more doubt about translation of covalently closed circRNA, the linearity of canonical mRNA is only theoretical: it has been shown for more than thirty years that polysomes exhibit a circular form and mRNA functional circularization has been demonstrated in the 1990s by the interaction of initiation factor eIF4G with poly(A) binding protein. More recently, additional mechanisms of 3′–5′ interaction have been reported, including m6A modification. Functional circularization enhances translation via ribosome recycling and acceleration of the translation initiation rate. This update of covalently and noncovalently closed circular mRNA translation landscape shows that RNA with circular shape might be the rule for translation with an important impact on disease development and biotechnological applications.
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