RNA-binding proteins (RBPs)

RNA-binding proteins (RBPs) are a diverse class of proteins that interact with various types of RNA to regulate gene expression post-transcriptionally, including processes such as splicing, polyadenylation, mRNA stability, and translation (Gerstberger et al., 2014). Many RBPs, such as the Musashi family (MSI1 and MSI2), are frequently overexpressed in cancers and are associated with the maintenance of cancer stem cells and resistance to therapy (Kharas et al., 2010). The small molecule Ro-08-2750 was originally identified as an antagonist of the p75 neurotrophin receptor (p75NTR) but was later found to bind the RNA-recognition motif (RRM) of MSI1, acting as a competitive inhibitor of its RNA-binding activity (Minohara et al., 2016). However, Ro-08-2750 is now recognized as a relatively non-specific inhibitor that targets multiple RRM-containing RBPs, which are often referred to as its off-targets. This lack of selectivity highlights a significant challenge in targeting RBPs, as broad inhibition of these proteins can lead to widespread disruption of RNA metabolism and significant cellular toxicity, complicating the development of RBP-targeted therapeutics.

Other names

RNA-binding protein familyRRM-containing proteinsMusashi-1 inhibitorsRo-08-2750 targetsRBPome

Inhibition of RNA-protein interactions (RPIs) by competitive binding to RNA-binding domains, such as RNA-recognition motifs (RRMs), preventing the protein from associating with its target mRNA transcripts.