Small molecule control of pre-mRNA splicing
Author(s) -
Brenton R. Graveley
Publication year - 2005
Publication title -
rna
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.037
H-Index - 171
eISSN - 1469-9001
pISSN - 1355-8382
DOI - 10.1261/rna.7229705
Subject(s) - rna splicing , sr protein , biology , spliceosome , exonic splicing enhancer , alternative splicing , protein splicing , polypyrimidine tract , microbiology and biotechnology , messenger rna , splicing factor , minigene , rna binding protein , precursor mrna , genetics , gene , rna
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.
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