A new article from the Lamond group, published in eLife, reports the identification of the plant biflavone, hinokiflavone, as a pre-mRNA splicing modulator (Pawellek et al., 2017). In collaboration with Ron Hay’s group in GRE and the group of Richard Hartley, (University of Glasgow), they show that both natural and synthetic hinokiflavone inhibits splicing in vitro by blocking spliceosome assembly, specifically preventing progression from the spliceosome complex A to complex B. Further, they find that hinokiflavone binds to and inhibits the SUMO protease, SENP1, in vitro and causes an increase in the levels of SUMO2-modified proteins in cellulo. Using an unbiased, SILAC MS-based proteomics assay, the major protein targets that are hyper-SUMOylated in cells treated with hinokiflavone were shown to include six proteins that are all components of the U2 snRNP spliceosome subunit that is required for A complex formation. This study identifies hinokiflavone as a potential novel cancer therapeutic and points to a role for protein SUMOylation in regulating spliceosome formation and alternative splicing.
Read the publication here.