丝氨酸/精氨酸富含结构域剪接因子（SRSF）指的是12种调节前体信使RNA剪接过程中剪接位点识别和剪接体组装的RNA结合蛋白。SRSF还参与其他RNA代谢事件，如转录、翻译和无义介导的降解，在细胞核和细胞质之间穿梭，从而在基因组多样性和细胞活动中起到不可或缺的作用。值得注意的是，异常的SRSF表达和/或突变会引发基因剪接的错误，导致致病基因和蛋白质亚型的产生，这突出了靶向SRSF治疗疾病的治疗潜力。在本综述中，我们更新了对SRSF结构和在RNA代谢中的功能的当前认识。然后，我们分析了SRSF诱导异常基因表达及其在癌症和非肿瘤性疾病中的致病结果。详细讨论了一些经过充分研究的SRSF抑制剂的开发情况。我们希望本综述能为SRSF功能研究和靶向SRSF药物开发的未来研究做出贡献。©2023中国药学会和中国医学科学院药物研究所。Elsevier B.V.负责生产和托管。

Serine/arginine-rich splicing factors (SRSFs) refer to twelve RNA-binding proteins which regulate splice site recognition and spliceosome assembly during precursor messenger RNA splicing. SRSFs also participate in other RNA metabolic events, such as transcription, translation and nonsense-mediated decay, during their shuttling between nucleus and cytoplasm, making them indispensable for genome diversity and cellular activity. Of note, aberrant SRSF expression and/or mutations elicit fallacies in gene splicing, leading to the generation of pathogenic gene and protein isoforms, which highlights the therapeutic potential of targeting SRSF to treat diseases. In this review, we updated current understanding of SRSF structures and functions in RNA metabolism. Next, we analyzed SRSF-induced aberrant gene expression and their pathogenic outcomes in cancers and non-tumor diseases. The development of some well-characterized SRSF inhibitors was discussed in detail. We hope this review will contribute to future studies of SRSF functions and drug development targeting SRSFs.© 2023 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.