RNA-binding protein (RBP)

RNA-binding proteins (RBPs) constitute a vast and diverse superfamily of over 1,500 proteins that interact with various forms of RNA to regulate post-transcriptional gene expression. These proteins act at every stage of the RNA life cycle, including splicing, polyadenylation, transport, stability, and translation, often by forming ribonucleoprotein (RNP) complexes. RBPs use specific motifs, such as the RNA recognition motif (RRM), Zinc finger, and KH domains, to recognize and bind their target transcripts in a sequence- or structure-dependent manner. Dysregulation, mutation, or aberrant aggregation of RBPs are hallmark features of numerous pathologies, most notably in cancers where they drive cell proliferation and metastasis, and in neurodegenerative diseases like Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD), where proteins like TDP-43 and FUS form toxic aggregates. In drug discovery, RBPs are increasingly recognized as viable therapeutic targets; current strategies include small molecule inhibitors to disrupt RBP-RNA interactions, antisense oligonucleotides (ASOs) to modulate splicing factors, and molecular glues to induce RBP degradation. While historically considered difficult to drug, successes in targeting RBPs for spinal muscular atrophy and various cancers underscore their potential as next-generation therapeutic focal points.

Other names

RNA-binding factorsRBPsRibonucleoproteinsRNA-binding domain-containing proteins

Splicing modulation (exon inclusion/skipping), inhibition of RNA-protein interaction, stabilization of target mRNA, translation inhibition, RNA demethylation inhibition, and sequestration of oncogenic RBPs.