Small molecule control of pre-mRNA splicing.
SR proteins regulate alternative splicing by binding to exonic sequences where, via an arginine/serine-rich splicing activation domain, they enhance the binding of the spliceosome to the adjacent splice sites. Here, a system is described in which a nontoxic derivative of the small molecule rapamycin is used to control pre-mRNA splicing in vitro. This involves the rapamycin-dependent recruitment of a splicing activation domain located on one protein to a second protein bound to the pre-mRNA. These results provide a new approach to explore for regulating gene expression in vivo with small molecules by controlling pre-mRNA splicing.
Graveley
Brenton R
BR
Department of Genetics and Developmental Biology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA. graveley@neuron.uchc.edu
D012322:RNA Precursors / Q000737:chemistry*; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics*; D020123:Sirolimus / Q000737:chemistry*
D012322:RNA Precursors; D012333:RNA, Messenger; D020123:Sirolimus