Figure 2.

Small-molecule-based therapeutic strategies targeting the alternative splicing environment. Various components of the cellular machinery mediating alternative RNA splicing can and are being targeted by small molecules to restore functionality. Common targets include PRMT5 or various type I PRMTs, snRNP U2, SF3b, and RBM-39. Abnormally expressed isoforms or aberrant proteins exhibiting gain-of-function effects enhancing tumor proliferation or survival can also themselves be the subject of small-molecule targeting. Abbreviations: pre-mRNA, pre-messenger RNA; PRMT, protein arginine methyltransferase; RBM-39, RNA-binding protein 39; SF3b, spliceosome factor 3b; and snRNP, small nuclear ribonucleoprotein. Red blunt arrows show negative regulation/inhibition.