title: A Challenging Pie to Splice: Drugging the Spliceosome.
abstract: Since its discovery in 1977, the study of alternative RNA splicing has revealed a plethora of mechanisms that had never before been documented in nature. Understanding these transitions and their outcome at the level of the cell and organism has become one of the great frontiers of modern chemical biology. Until 2007, this field remained in the hands of RNA biologists. However, the recent identification of natural product and synthetic modulators of RNA splicing has opened new access to this field, allowing for the first time a chemical-based interrogation of RNA splicing processes. Simultaneously, we have begun to understand the vital importance of splicing in disease, which offers a new platform for molecular discovery and therapy. As with many natural systems, gaining clear mechanistic detail at the molecular level is key towards understanding the operation of any biological machine. This minireview presents recent lessons learned in this emerging field of RNA splicing chemistry and chemical biology.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0358, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: León
authors.affiliation: Moores Cancer Center and Department of Medicine, University of California, San Diego, La Jolla, CA, 92093-0820, USA.
authors.forename: Manoj K
authors.initials: MK
authors.lastname: Kashyap
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0358, USA.
authors.forename: Warren C
authors.initials: WC
authors.lastname: Chan
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0358, USA.
authors.forename: Kelsey A
authors.initials: KA
authors.lastname: Krug
authors.affiliation: Moores Cancer Center and Department of Medicine, University of California, San Diego, La Jolla, CA, 92093-0820, USA.
authors.forename: Januario E
authors.initials: JE
authors.lastname: Castro
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0358, USA.
authors.forename: James J
authors.identifier: 0000-0001-6500-4107
authors.initials: JJ
authors.lastname: La Clair
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0358, USA.
authors.forename: Michael D
authors.identifier: 0000-0002-4472-2254
authors.initials: MD
authors.lastname: Burkart
mesh_terms: D017398:Alternative Splicing / Q000187:drug effects*; D001688:Biological Products / Q000737:chemistry; D006801:Humans; D017381:Spliceosomes / Q000187:drug effects*
chemical_list: D001688:Biological Products
keywords: RNA splicing; chemical biology; drug discovery; inhibitors; spliceosome