环状RNA翻译的分子机制-动脉网

Molecular mechanisms of circular RNA translation

Nature 等信源发布 2024-06-14 10:50

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AbstractCircular RNAs (circRNAs) are covalently closed single-stranded RNAs without a 5′ cap structure and a 3′ poly(A) tail typically present in linear mRNAs of eukaryotic cells. CircRNAs are predominantly generated through a back-splicing process within the nucleus. CircRNAs have long been considered non-coding RNAs seemingly devoid of protein-coding potential.

摘要环状RNA（circRNA）是共价闭合的单链RNA，没有5'帽结构和3'聚（a）尾，通常存在于真核细胞的线性mRNA中。circRNA主要通过细胞核内的反向剪接过程产生。长期以来，circRNA被认为是非编码RNA，似乎缺乏蛋白质编码潜力。

However, many recent studies have challenged this idea and have provided substantial evidence that a subset of circRNAs can associate with polysomes and indeed be translated. Therefore, in this review, we primarily highlight the 5’ cap-independent internal initiation of translation that occurs on circular RNAs.

然而，最近的许多研究挑战了这一观点，并提供了大量证据表明circRNA的一个子集可以与多核糖体结合并确实可以翻译。因此，在这篇综述中，我们主要强调了在环状RNA上发生的5'cap独立的内部翻译起始。

Several molecular features of circRNAs, including the internal ribosome entry site, N6-methyladenosine modification, and the exon junction complex deposited around the back-splicing junction after back-splicing event, play pivotal roles in their efficient internal translation. We also propose a possible relationship between the translatability of circRNAs and their stability, with a focus on nonsense-mediated mRNA decay and nonstop decay, both of which are well-characterized mRNA surveillance mechanisms.

circRNA的几个分子特征，包括内部核糖体进入位点，N6-甲基腺苷修饰以及在反向剪接事件后沉积在反向剪接连接周围的外显子连接复合物，在其有效的内部翻译中起关键作用。我们还提出了circRNA的可翻译性与其稳定性之间的可能关系，重点是无义介导的mRNA衰变和不间断衰变，这两者都是特征明确的mRNA监测机制。

An in-depth understanding of circRNA translation will reshape and expand our current knowledge of proteomics..

对circRNA翻译的深入理解将重塑和扩展我们目前对蛋白质组学的知识。。

IntroductionIn eukaryotic cells, circular RNAs (circRNAs) are produced primarily by back-splicing events of pre-mRNAs1. Nascent pre-mRNAs are produced by RNA polymerase II and undergo multiple processing steps in the nucleus, including 5′-capping, 3′-polyadenylation, and splicing. Splicing removes introns and ligates consecutive neighboring exons to generate a mature messenger RNA (mRNA).

引言在真核细胞中，环状RNA（circRNA）主要由pre-mRNAs1的反向剪接事件产生。新生的前mRNA由RNA聚合酶II产生，并在细胞核中经历多个加工步骤，包括5'-加帽，3'-聚腺苷酸化和剪接。剪接去除内含子并连接连续的相邻外显子以产生成熟的信使RNA（mRNA）。

Notably, not all splicing processes occur between exons located in close proximity in terms of nucleotide sequences. Specific features of nucleotides in introns flanking exons facilitate RNA looping, which causes the downstream 5′ splice site (splice donor) to be in close proximity to the upstream 3′ splice site (splice acceptor).

值得注意的是，并非所有剪接过程都发生在核苷酸序列非常接近的外显子之间。外显子侧翼内含子中核苷酸的特定特征有助于RNA环化，从而导致下游5'剪接位点（剪接供体）与上游3'剪接位点（剪接受体）非常接近。

These features include inverted repeats or nucleotide sequences that interact with RNA-binding proteins (RBPs) with dimerization ability. Spatial proximity between exon termini triggers an alternative noncanonical mode of splicing (termed back-splicing) and allows the biogenesis of circRNAs that are covalently closed structures and possess a head-to-tail connected single-stranded structure2.

这些特征包括与具有二聚化能力的RNA结合蛋白（RBP）相互作用的反向重复序列或核苷酸序列。外显子末端之间的空间接近触发了另一种非规范剪接模式（称为反向剪接），并允许circRNA的生物发生，这些circRNA是共价闭合结构，具有头尾连接的单链结构2。

Due to the lack of both a 5′ cap and a 3′ poly(A) tail, circRNAs are generally resistant to exoribonuclease attack and exhibit greater stability than that of the cognate linear mRNAs with identical nucleotide sequences.In this review, we provide an overview of the various methods for circRNA biogenesis and summarize the diverse molecular functions of circRNAs, including their roles as microRNA (miRNA) sponges, protein regulators, and templates for protein synthesis.

由于缺乏5'帽和3'poly（a）尾，circRNA通常对核糖核酸酶攻击具有抗性，并且比具有相同核苷酸序列的同源线性mRNA表现出更高的稳定性。在这篇综述中，我们概述了circRNA生物发生的各种方法，并总结了circRNA的多种分子功能，包括它们作为microRNA（miRNA）海绵，蛋白质调节剂和蛋白质合成模板的作用。

Next, we examine the molecular details of circRNA translation and consider the possible relationship between circRNA translation and circRNA stability.CircRNA biogenesisMost eukaryotic circRNAs are produced vi.

接下来，我们检查circRNA翻译的分子细节，并考虑circRNA翻译与circRNA稳定性之间的可能关系。CircRNA生物发生大多数真核生物CircRNA产生于vi。

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Download referencesAcknowledgementsThis work was supported by the National Research Foundation (NRF) of Korea (NRF-2015R1A3A2033665, NRF-2018R1A5A1024261, and NRF-2022M3E5F1017965 to Y.K.K.; and RS-2023-00242239 to H.J.H.).Author informationAuthors and AffiliationsDepartment of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 34141, Republic of KoreaHyun Jung Hwang & Yoon Ki KimAuthorsHyun Jung HwangView author publicationsYou can also search for this author in.

下载参考文献致谢这项工作得到了韩国国家研究基金会（NRF）的支持（Y.K.K.的NRF-2015R1A3A2033665，NRF-2018R1A5A1024261和NRF-2022M3E5F1017965；以及H.J.H.的RS-2023-00242239）。作者信息作者和附属机构韩国高级科学技术研究所生物科学系，大田，34141，大韩民国Hyun Jung Hwang＆Yoon Ki Kim作者Hyun Jung Hwang View作者出版物您也可以在中搜索这位作者。

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PubMed Google ScholarContributionsY.K.K. conceptualized the manuscript. H.J.H. and Y.K.K. conducted literature reviews, drafted the manuscript, and participated in its revision and editing. H.J.H. prepared the figures.Corresponding authorCorrespondence to

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Reprints and permissionsAbout this articleCite this articleHwang, H.J., Kim, Y.K. Molecular mechanisms of circular RNA translation.

转载和许可本文引用本文Hwang，H.J.，Kim，Y.K。环状RNA翻译的分子机制。

Exp Mol Med (2024). https://doi.org/10.1038/s12276-024-01220-3Download citationReceived: 10 December 2023Revised: 22 February 2024Accepted: 23 February 2024Published: 14 June 2024DOI: https://doi.org/10.1038/s12276-024-01220-3Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

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