Antisense oligonucleotides effectively inhibit the co-transcriptional splicing of a Candida group I intron in vitro and in vivo: Implications for antifungal therapeutics

Libin Zhang, Michael J Leibowitz, Yi Zhang

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)734-738
Number of pages5
JournalFEBS Letters
Volume583
Issue number4
DOIs
StatePublished - Feb 18 2009
Externally publishedYes

Fingerprint

Candida
Antisense Oligonucleotides
Introns
Catalytic RNA
Candida albicans
RNA
Therapeutics
Flow cytometry
Flow Cytometry
Cells
In Vitro Techniques
Growth
Pharmaceutical Preparations
Experiments

Keywords

  • Antimicrobial
  • Antisense oligonucleotide (AON)
  • Candida albicans
  • Group I ribozyme
  • P3-P7 core

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Genetics
  • Molecular Biology
  • Structural Biology

Cite this

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abstract = "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.",
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AU - Zhang, Yi

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