Direct circRNA-mRNA Binding Controls mRNA Fate: A New Mechanism for circRNAs.

IF 3.6 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Non-Coding RNA Pub Date : 2025-07-18 DOI:10.3390/ncrna11040053

Raffaele Garraffo, Manuel Beltran Nebot

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引用次数: 0

Abstract

Circular RNAs (circRNAs) are covalently closed RNA molecules generated through a non-canonical splicing event known as back-splicing. This particular class of non-coding RNAs has attracted growing interest due to its evolutionary conservation across eukaryotes, high expression in the central nervous system, and frequent dysregulation in various pathological conditions, including cancer. Traditionally, circRNAs have been characterised by their ability to function as microRNA (miRNA) and protein sponges. However, recent discoveries from multiple research groups have uncovered a novel and potentially transformative mechanism of action: the direct interaction of circRNAs with messenger RNAs (mRNAs) to regulate their fate. These interactions can influence mRNA stability and translation, revealing a new layer of post-transcriptional gene regulation. In this review, we present and analyse the latest evidence supporting the emerging role of circRNAs in diverse biological contexts. We highlight the growing body of research demonstrating circRNA-mRNA interactions as a functional regulatory mechanism and explore their involvement in key physiological and pathophysiological processes. Understanding this novel mechanism expands our knowledge of RNA-based regulation and opens new opportunities for therapeutic strategies targeting circRNA-mRNA networks in human disease.

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circRNA-mRNA直接结合控制mRNA命运：circrna的新机制。

环状RNA （circRNAs）是一种共价封闭的RNA分子，通过被称为反剪接的非规范剪接事件产生。由于其在真核生物中的进化保守性、在中枢神经系统中的高表达以及在包括癌症在内的各种病理条件下的频繁失调，这类特殊的非编码rna引起了人们越来越多的兴趣。传统上，circrna的特点是它们具有作为microRNA （miRNA）和蛋白质海绵的功能。然而，最近多个研究小组的发现揭示了一种新的、潜在的变革性作用机制：circRNAs与信使rna （mrna）的直接相互作用来调节它们的命运。这些相互作用可以影响mRNA的稳定性和翻译，揭示了转录后基因调控的新层面。在这篇综述中，我们提出并分析了支持环状rna在不同生物学背景下新兴作用的最新证据。我们强调越来越多的研究表明circRNA-mRNA相互作用是一种功能调节机制，并探讨了它们在关键生理和病理生理过程中的参与。了解这种新机制扩展了我们对rna调控的认识，并为针对人类疾病的circRNA-mRNA网络的治疗策略开辟了新的机会。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Non-Coding RNA Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

6.70

自引率

4.70%

发文量

审稿时长

10 weeks

期刊介绍： Functional studies dealing with identification, structure-function relationships or biological activity of: small regulatory RNAs (miRNAs, siRNAs and piRNAs) associated with the RNA interference pathway small nuclear RNAs, small nucleolar and tRNAs derived small RNAs other types of small RNAs, such as those associated with splice junctions and transcription start sites long non-coding RNAs, including antisense RNAs, long ''intergenic'' RNAs, intronic RNAs and ''enhancer'' RNAs other classes of RNAs such as vault RNAs, scaRNAs, circular RNAs, 7SL RNAs, telomeric and centromeric RNAs regulatory functions of mRNAs and UTR-derived RNAs catalytic and allosteric (riboswitch) RNAs viral, transposon and repeat-derived RNAs bacterial regulatory RNAs, including CRISPR RNAS Analysis of RNA processing, RNA binding proteins, RNA signaling and RNA interaction pathways: DICER AGO, PIWI and PIWI-like proteins other classes of RNA binding and RNA transport proteins RNA interactions with chromatin-modifying complexes RNA interactions with DNA and other RNAs the role of RNA in the formation and function of specialized subnuclear organelles and other aspects of cell biology intercellular and intergenerational RNA signaling RNA processing structure-function relationships in RNA complexes RNA analyses, informatics, tools and technologies: transcriptomic analyses and technologies development of tools and technologies for RNA biology and therapeutics Translational studies involving long and short non-coding RNAs: identification of biomarkers development of new therapies involving microRNAs and other ncRNAs clinical studies involving microRNAs and other ncRNAs.