Issue Date: July 23, 2007
Small Molecules Disrupt RNA Splicing
The identification of the first small molecules capable of disrupting the work of the spliceosome promises new insight into how this crucial biological machine helps convert DNA into proteins (Nat. Chem. Biol., DOI: 10.1038/nchembio.2007.16 and 10.1038/nchembio.2007.18). Before raw RNA transcripts of protein-coding genes can be converted into protein, the spliceosome must remove any unwanted and intervening RNA segments. Failure to splice out such intervening sequences, commonly called introns, before translation gives rise to flawed and potentially dangerous proteins. Independent teams led by Minoru Yoshida of Japanese research institute RIKEN and Yoshiharu Mizui of Japanese drugmaker Eisai show that the antitumor natural products FR901464 and pladienolide, respectively, are potent inhibitors of a key component of the spliceosome. Eisai currently has a pladienolide derivative in Phase I clinical trials for various cancers. The findings suggest that the spliceosome is a promising target for anticancer drug design, the authors note.
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