Chemical Modulation of Pre-mRNA Splicing in Mammalian Systems.

RNA splicing is a key component of gene expression and proteomic diversity in humans. The spliceosome assembles on and processes individual nascent pre-mRNA transcripts into distinct mature mRNAs that can code for different proteins. Splicing programs can be affected by somatic mutations and changes in response to exogenous stimuli. Importantly, alterations in splicing can be direct drivers of diseases including cancers. This Review describes recent advances and the potential for targeting and controlling pre-mRNA splicing in humans with small molecules, ranging from targeting spliceosomal proteins to direct targeting of individual RNA transcripts.