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Anti-infective nitazoxanide disrupts transcription of ribosome biogenesis-related genes in yeast

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Abstract

Background

Nitazoxanide is a broad-spectrum, anti-parasitic, anti-protozoal, anti-viral drug, whose mechanisms of action have remained elusive.

Objective

In this study, we aimed to provide insight into the mechanisms of action of nitazoxanide and the related eukaryotic host responses by characterizing transcriptome profiles of Saccharomyces cerevisiae exposed to nitazoxanide.

Methods

RNA-Seq was used to investigate the transcriptome profiles of three strains of S. cerevisiae with dsRNA virus-like elements, including a strain that hosts M28 encoding the toxic protein K28. From the strain with M28, an additional sub-strain was prepared by excluding M28 using a nitazoxanide treatment.

Results

Our transcriptome analysis revealed the effects of nitazoxanide on ribosome biogenesis. Many genes related to the UTP A, UTP B, Mpp10-Imp3-Imp4, and Box C/D snoRNP complexes were differentially regulated by nitazoxanide exposure in all of the four tested strains/sub-strains. Examples of the differentially regulated genes included UTP14, UTP4, NOP4, UTP21, UTP6, and IMP3. The comparison between the M28-laden and non-M28-laden sub-strains showed that the mitotic cell cycle was more significantly affected by nitazoxanide exposure in the non-M28-laden sub-strain.

Conclusions

Overall, our study reveals that nitazoxanide disrupts regulation of ribosome biogenesis-related genes in yeast.

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Acknowledgements

This research was supported by the Small Grant for Exploratory Research (SGER) Program of the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (2015R1D1A1A02061903).

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  1. Siyu Xu

    Present address: State Key Joint Laboratory of Environmental Simulation and Pollution Control, College of Environmental Sciences and Engineering, Peking University, Beijing, 100871, China

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  1. Department of Environmental Health Sciences, Graduate School of Public Health, Seoul National University, Seoul, 08826, South Korea

    Siyu Xu & Naomichi Yamamoto

  2. Institute of Health and Environment, Graduate School of Public Health, Seoul National University, Seoul, 08826, South Korea

    Naomichi Yamamoto

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Xu, S., Yamamoto, N. Anti-infective nitazoxanide disrupts transcription of ribosome biogenesis-related genes in yeast. Genes Genom 42, 915–926 (2020). https://doi.org/10.1007/s13258-020-00958-0

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