Enediyne-mediated cleavage of RNA

Abstract

RNA cleavage by enediyne anticancer antibiotics was shown to occur with no apparent sequence selectivity, but RNA structure appears to be important in those substrates where cleavage was observed. Neocarzinostatin (NCS) cleaved a wider variety of RNA substrates than either esperamicin (ESP) or calicheamicin (CAL), and dynemicin (DYN) has yet to cleave any RNA substrate tried. NCS, ESP, and CAL were all observed to cleave RNA substrates near the 5'-end, and all three compounds exhibited cleavage in single-stranded loop regions of the RNA substrates. NCS required no thiol for activation and subsequent cleavage, but ESP and CAL required addition of thiol, as expected, for cleavage to occur. An RNA hairpin substrate containing a UCCU sequence, equivalent to the TCCT sequence preferred by CAL in double-stranded DNA substrates, was cleaved by CAL, but no retention of selectivity for the UCCU site was retained by CAL in this RNA substrate. This study confirms an earlier observation that RNA is a substrate for enediyne cleavage, and indicates that nucleic acid cleaving compounds such as the enediynes could be useful probes of RNA three-dimensional structure.