RBFOX2: An RNA-binding protein with alternative splicing and non-alternative splicing regulatory functions

RNA-binding Fox-1 homolog 2 (RBFOX2) is a key RNA-binding protein that primarily functions by regulating alternative splicing. Furthermore, RBFOX2 regulates RNA metabolism across the transcriptional and multiple post-transcriptional stages, encompassing recognizing RNA epigenetic modifications, inhibiting transcription, regulating alternative polyadenylation, inhibiting miRNA processing, and stabilizing mRNA. Additionally, RBFOX2 is regulated by upstream factors such as RNA binding proteins, non-coding RNAs, and transcription factors. RBFOX2 is extensively involved in the regulation of development and the maintenance of physiological functions. The dysregulation of RBFOX2 is closely associated with tumors, cardiovascular diseases, developmental defects and metabolic diseases. In this review, we summarize the regulatory functions of RBFOX2 in terms of both alternative and non-alternative splicing, the upstream regulatory factors of RBFOX2, and its relationship with disease etiology and progression, with the aim of providing a comprehensive understanding of the role of RBFOX2 and offering new insights for the study of RBFOX2. • RBFOX2 is a key RNA binding protein that regulates alternative splicing in a position-dependent manner. • The RBFOX2-mediated alternative splicing affects multiple cellular biological processes. • RBFOX2 is also a multifunctional protein regulates RNA metabolism at multiple levels. • Multiple regulators regulate the expression of RBFOX2 or affect its function.