RNA-binding protein 4 (RBM4)

RNA-binding protein 4 (RBM4), also known as Dynorphin A-binding factor (DBF), is a multifunctional post-transcriptional regulator that plays a critical role in alternative splicing and translation control [4, 5]. It was originally cloned based on its high-affinity binding to the endogenous opioid peptide Dynorphin A, although its primary biological functions are centered on orchestrating splicing cascades rather than classical opioid signaling [1, 11]. RBM4 acts as a potent tumor suppressor in various malignancies, including colorectal and lung cancers, by promoting the expression of pro-apoptotic splice variants (e.g., MCL1S) and antagonizing oncogenic splicing factors like SRSF1 [5, 7]. Beyond oncology, RBM4 is essential for metabolic health, as it regulates the splicing of the insulin receptor to favor the insulin-sensitive B-isoform; its downregulation is associated with the development of Type 2 diabetes [4, 8]. While currently considered a high-value target for RNA-modulating and splicing-correction therapies, there are no approved drugs that specifically target RBM4 [8, 12].

Other names

Dynorphin A-binding factorDBFRNA binding motif protein 4RNA-binding protein 4RBM4AZinc finger CCHC-type and RNA-binding motif-containing protein 3ALark homolog

Modulation of alternative pre-mRNA splicing and translation through binding to CU-rich RNA elements and recruitment of the spliceosome or translation initiation machinery [4, 7, 8].