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Antisense oligonucleotides effectively inhibit the co‐transcriptional splicing of a Candida group I intron in vitro and in vivo: Implications for antifungal therapeutics
Author(s) -
Zhang Libin,
Leibowitz Michael J.,
Zhang Yi
Publication year - 2009
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2009.01.040
Subject(s) - rna splicing , in vivo , intron , in vitro , oligonucleotide , antifungal , chemistry , group ii intron , biology , gene , biochemistry , microbiology and biotechnology , genetics , rna
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.