Antisense oligonucleotides effectively inhibit the co-transcriptional splicing of a Candida group I intron in vitro and in vivo: Implications for antifungal therapeutics.
Self-splicing of group I intron from the 26S rRNA of Candida albicans is essential for maturation of the host RNA. Here, we demonstrated that the co-transcriptional splicing of the intron in vitro was blocked by antisense oligonucleotides (AONs) targeting the P3-P7 core of the intron. The core-targeted AON effectively and specifically inhibited the intron splicing from its host RNA in living C. albicans. Furthermore, flow cytometry experiments showed that the growth inhibition was caused by a fungicidal effect. For the first time, we showed that an AON targeting the ribozyme core folding specifically inhibits the endogenous ribozyme splicing in living cells and specifically kills the intron-containing fungal strains, which sheds light on the development of antifungal drugs in the future.
Zhang
Libin
L
State Key Laboratory of Virology and Department of Biochemistry and Molecular Biology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.
Leibowitz
Michael J
MJ
Zhang
Yi
Y
D000935:Antifungal Agents / Q000494:pharmacology / Q000627:therapeutic use; D002176:Candida albicans / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development* / Q000302:isolation & purification; D004305:Dose-Response Relationship, Drug; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D007438:Introns / Q000187:drug effects*; D007700:Kinetics; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D012326:RNA Splicing / Q000187:drug effects* / Q000235:genetics; D016337:RNA, Catalytic / Q000235:genetics / Q000378:metabolism
D000935:Antifungal Agents; D005456:Fluorescent Dyes; D016376:Oligonucleotides, Antisense; D016337:RNA, Catalytic; D016650:Fluorescein-5-isothiocyanate