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RNA 剪接因子 RBFOX2 是癌症和心肌病进展的关键因素。

RNA splicing factor RBFOX2 is a key factor in the progression of cancer and cardiomyopathy.

机构信息

Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou, China.

Medical Genetics Center, School of Medicine, Ningbo University, Ningbo, China.

出版信息

Clin Transl Med. 2024 Sep;14(9):e1788. doi: 10.1002/ctm2.1788.

Abstract

BACKGROUND

Alternative splicing of pre-mRNA is a fundamental regulatory process in multicellular eukaryotes, significantly contributing to the diversification of the human proteome. RNA-binding fox-1 homologue 2 (RBFOX2), a member of the evolutionarily conserved RBFOX family, has emerged as a critical splicing regulator, playing a pivotal role in the alternative splicing of pre-mRNA. This review provides a comprehensive analysis of RBFOX2, elucidating its splicing activity through direct and indirect binding mechanisms. RBFOX2 exerts substantial influence over the alternative splicing of numerous transcripts, thereby shaping essential cellular processes such as differentiation and development.

MAIN BODY OF THE ABSTRACT

Dysregulation of RBFOX2-mediated alternative splicing has been closely linked to a spectrum of cardiovascular diseases and malignant tumours, underscoring its potential as a therapeutic target. Despite significant progress, current research faces notable challenges. The complete structural characterisation of RBFOX2 remains elusive, limiting in-depth exploration beyond its RNA-recognition motif. Furthermore, the scarcity of studies focusing on RBFOX2-targeting drugs poses a hindrance to translating research findings into clinical applications.

CONCLUSION

This review critically assesses the existing body of knowledge on RBFOX2, highlighting research gaps and limitations. By delineating these areas, this analysis not only serves as a foundational reference for future studies but also provides strategic insights for bridging these gaps. Addressing these challenges will be instrumental in unlocking the full therapeutic potential of RBFOX2, paving the way for innovative and effective treatments in various diseases.

摘要

背景

前体 mRNA 的可变剪接是真核多细胞生物的基本调控过程,对人类蛋白质组的多样化有重要贡献。RNA 结合 Fox-1 同源物 2(RBFOX2)是进化上保守的 RBFOX 家族的一员,作为关键的剪接调控因子,在前体 mRNA 的可变剪接中发挥着关键作用。本综述对 RBFOX2 进行了全面分析,通过直接和间接结合机制阐明了其剪接活性。RBFOX2 对许多转录本的可变剪接产生了巨大影响,从而塑造了分化和发育等重要的细胞过程。

摘要正文

RBFOX2 介导的可变剪接失调与一系列心血管疾病和恶性肿瘤密切相关,突显了其作为治疗靶点的潜力。尽管取得了重大进展,但当前的研究仍面临着显著的挑战。RBFOX2 的完整结构特征仍然难以捉摸,限制了对其 RNA 识别基序以外的深入探索。此外,缺乏针对 RBFOX2 靶向药物的研究也阻碍了将研究成果转化为临床应用。

结论

本综述批判性地评估了关于 RBFOX2 的现有知识体系,强调了研究差距和局限性。通过描绘这些领域,本分析不仅为未来的研究提供了基础性参考,还为弥合这些差距提供了战略见解。解决这些挑战对于充分发挥 RBFOX2 的治疗潜力至关重要,为各种疾病的创新和有效治疗铺平了道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9260/11380049/98a934800893/CTM2-14-e1788-g001.jpg

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