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Regulation of Splicing by Clinical Drugs

ABSTRACT: Alternative splicing analysis after treatment with three clinically aproved drugs Bioactive compounds have been invaluable for dissecting the mechanisms, regulation and functions of cellular processes. However, very few such reagents have been described for pre-mRNA splicing. To facilitate their systematic discovery, we developed a high throughput cell-based assay that measures pre-mRNA splicing utilizing a quantitative reporter system with advantageous features. The reporter, consisting of a destabilized, intron-containing luciferase expressed from a short-lived mRNA, allows rapid screens (<4 hr) thereby obviating potential toxicity of splicing inhibitors. We describe three inhibitors (out of >23,000 screened), all pharmacologically active: clotrimazole, flunarizine and chlorhexidine. Interestingly, none was a general splicing inhibitor. Rather, each caused distinct splicing changes of numerous genes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE19891 | GEO | 2010/02/28

SECONDARY ACCESSION(S): PRJNA122033

REPOSITORIES: GEO

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