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反向剪接调控的分子基础及其在调控环形RNA水平中的应用。

Molecular basis of backsplicing regulation and its application to manipulate circRNA levels.

作者信息

Wang Yucong, Dzakah Emmanuel Enoch, Wang Xiaolin

机构信息

Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, The RNA Institute, School of Basic Medical Sciences, Division of Life Science and Medicine, University of Science and Technology of China, Hefei, China.

Clinical Research Center, Guangdong Clifford Hospital, Guangzhou, China.

出版信息

RNA Biol. 2025 Dec;22(1):1-10. doi: 10.1080/15476286.2025.2525914. Epub 2025 Jun 27.

DOI:10.1080/15476286.2025.2525914
PMID:40575920
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12218527/
Abstract

Circular RNAs (circRNAs) are covalently closed single-stranded RNA molecules, which have been implicated in both physiology and human diseases. Most circRNAs are typically generated through backsplicing, where a downstream splice donor is covalently joined to an upstream splice acceptor. Backsplicing is dependent on the spliceosome machinery and is precisely controlled by various -elements and -factors. In the present review, we summarize the molecular mechanisms of backsplicing regulation as well as their physiological and pathological significance. Additionally, we discuss the strategies to manipulate circRNA expression and , aiming to explore the application of circRNA biogenesis in the diagnosis and therapy of human diseases.

摘要

环状RNA(circRNAs)是共价闭合的单链RNA分子,其与生理功能和人类疾病均有关联。大多数circRNAs通常通过反向剪接产生,即下游剪接供体与上游剪接受体共价连接。反向剪接依赖于剪接体机制,并受到多种元件和因子的精确调控。在本综述中,我们总结了反向剪接调控的分子机制及其生理和病理意义。此外,我们还讨论了调控circRNA表达的策略,旨在探索circRNA生物合成在人类疾病诊断和治疗中的应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5580/12218527/c9f9cc0785bf/KRNB_A_2525914_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5580/12218527/ac945aec75f2/KRNB_A_2525914_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5580/12218527/68b2da7cc407/KRNB_A_2525914_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5580/12218527/91a3465abe8f/KRNB_A_2525914_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5580/12218527/c9f9cc0785bf/KRNB_A_2525914_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5580/12218527/ac945aec75f2/KRNB_A_2525914_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5580/12218527/68b2da7cc407/KRNB_A_2525914_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5580/12218527/91a3465abe8f/KRNB_A_2525914_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5580/12218527/c9f9cc0785bf/KRNB_A_2525914_F0004_OC.jpg

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本文引用的文献

1
Fast Degradation of MecciRNAs by SUPV3L1/ELAC2 Provides a Novel Opportunity to Tackle Heart Failure With Exogenous MecciRNA.SUPV3L1/ELAC2对MecciRNAs的快速降解为通过外源性MecciRNA治疗心力衰竭提供了新机会。
Circulation. 2025 Apr 29;151(17):1272-1290. doi: 10.1161/CIRCULATIONAHA.124.070840. Epub 2025 Feb 20.
2
The therapeutic potential of circular RNAs.环状RNA的治疗潜力。
Nat Rev Genet. 2025 Apr;26(4):230-244. doi: 10.1038/s41576-024-00806-x. Epub 2025 Jan 9.
3
ZC3H14 facilitates backsplicing by binding to exon-intron boundary and 3' UTR.
ZC3H14 通过结合外显子-内含子边界和 3' UTR 促进剪接。
Mol Cell. 2024 Nov 21;84(22):4314-4333.e9. doi: 10.1016/j.molcel.2024.10.001. Epub 2024 Oct 25.
4
HNRNPD regulates the biogenesis of circRNAs and the ratio of mRNAs to circRNAs for a set of genes.HNRNPD 调节 circRNAs 的生物发生和一组基因中转录本与 circRNAs 的比例。
RNA Biol. 2024 Jan;21(1):1-15. doi: 10.1080/15476286.2024.2386500. Epub 2024 Aug 24.
5
Systematic loss-of-function screens identify pathway-specific functional circular RNAs.系统的功能丧失筛选鉴定出具有特定通路功能的环状 RNA。
Nat Cell Biol. 2024 Aug;26(8):1359-1372. doi: 10.1038/s41556-024-01467-y. Epub 2024 Aug 2.
6
Circular RNA in cancer.环状 RNA 与癌症。
Nat Rev Cancer. 2024 Sep;24(9):597-613. doi: 10.1038/s41568-024-00721-7. Epub 2024 Jul 29.
7
Functional roles of conserved lncRNAs and circRNAs in eukaryotes.保守的长链非编码RNA和环状RNA在真核生物中的功能作用。
Noncoding RNA Res. 2024 Jun 25;9(4):1271-1279. doi: 10.1016/j.ncrna.2024.06.014. eCollection 2024 Dec.
8
Decoding protein-RNA interactions using CLIP-based methodologies.利用基于 CLIP 的方法解码蛋白质-RNA 相互作用。
Nat Rev Genet. 2024 Dec;25(12):879-895. doi: 10.1038/s41576-024-00749-3. Epub 2024 Jul 9.
9
Inverted Alu repeats: friends or foes in the human transcriptome.反向 Alu 重复序列:人类转录组中的朋友还是敌人?
Exp Mol Med. 2024 Jun;56(6):1250-1262. doi: 10.1038/s12276-024-01177-3. Epub 2024 Jun 14.
10
Systematic identification and characterization of exon-intron circRNAs.外显子-内含子环状RNA的系统鉴定与表征
Genome Res. 2024 Apr 25;34(3):376-393. doi: 10.1101/gr.278590.123.