背景:前mRNA的可变剪接是多细胞真核生物的基本调节过程,显着促进人类蛋白质组的多样化。RNA结合fox-1同源物2(RBFOX2),进化保守的RBFOX家族的成员,已经成为关键的拼接调节剂,在前mRNA的可变剪接中起关键作用。这篇综述提供了对RBFOX2的全面分析,阐明了其通过直接和间接结合机制的剪接活性。RBFOX2对许多转录物的可变剪接产生重大影响,从而塑造必要的细胞过程,如分化和发育。
■RBFOX2介导的可变剪接的失调与一系列心血管疾病和恶性肿瘤密切相关,强调其作为治疗靶点的潜力。尽管取得了重大进展,当前的研究面临着显著的挑战。RBFOX2的完整结构表征仍然难以捉摸,限制了其RNA识别基序之外的深入探索。此外,针对RBFOX2靶向药物的研究缺乏,阻碍了将研究成果转化为临床应用.
结论:这篇综述严格评估了现有的RBFOX2知识体系,强调了研究的差距和局限性。通过划定这些区域,这一分析不仅为未来研究提供了基础参考,也为弥合这些差距提供了战略见解。应对这些挑战将有助于释放RBFOX2的全部治疗潜力,为各种疾病的创新和有效治疗铺平道路。
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.
UNASSIGNED: 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.
CONCLUSIONS: 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.