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Rtf1 HMD domain facilitates global histone H2B monoubiquitination and regulates morphogenesis and virulence in the meningitis-causing pathogen Cryptococcus neoformans

Yixuan Jiang, Fujie Zhao, Ying Liang, Zhenguo Lu, Siyu Wang, Yao Meng, Zhanxiang Liu, Jing Zhang, View ORCID ProfileYoubao Zhao
doi: https://doi.org/10.1101/2024.05.20.594937
Yixuan Jiang
1College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan 450046, China
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Fujie Zhao
1College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan 450046, China
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Ying Liang
1College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan 450046, China
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Zhenguo Lu
1College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan 450046, China
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Siyu Wang
1College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan 450046, China
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Yao Meng
1College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan 450046, China
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Zhanxiang Liu
1College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan 450046, China
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Jing Zhang
1College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan 450046, China
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  • For correspondence: [email protected] [email protected]
Youbao Zhao
1College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan 450046, China
2Key Laboratory of Quality and Safety Control of Poultry Products, Ministry of Agriculture and Rural Affairs, Zhengzhou, Henan 450046, China
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  • ORCID record for Youbao Zhao
  • For correspondence: [email protected] [email protected]
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Abstract

Rtf1 is generally considered to be a subunit of the Paf1 complex (Paf1C), which is a multifunctional protein complex involved in histone modification and RNA biosynthesis at multiple stages. Rtf1 is stably associated with the Paf1C in Saccharomyces cerevisiae, but not in other species including humans. Little is known about its function in human fungal pathogens. Here, we show that Rtf1 is required for facilitating H2B monoubiquitination (H2Bub1), and regulates fungal morphogenesis and pathogenicity in the meningitis-causing fungal pathogen Cryptococcus neoformans. Rtf1 is not tightly associated with the Paf1C, and its histone modification domain (HMD) is sufficient to promote H2Bub1 and the expression of genes related to fungal mating and filamentation. Moreover, Rtf1 HMD fully restores fungal morphogenesis and pathogenicity; however, it fails to restore defects of thermal tolerance and melanin production in the rtf1Δ strain background. The present study establishes a role for cryptococcal Rtf1 as a Paf1C-independent regulator in regulating fungal morphogenesis and pathogenicity, and highlights the function of HMD in facilitating global H2Bub1 in C. neoformans.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted May 20, 2024.
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Rtf1 HMD domain facilitates global histone H2B monoubiquitination and regulates morphogenesis and virulence in the meningitis-causing pathogen Cryptococcus neoformans
Yixuan Jiang, Fujie Zhao, Ying Liang, Zhenguo Lu, Siyu Wang, Yao Meng, Zhanxiang Liu, Jing Zhang, Youbao Zhao
bioRxiv 2024.05.20.594937; doi: https://doi.org/10.1101/2024.05.20.594937
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Rtf1 HMD domain facilitates global histone H2B monoubiquitination and regulates morphogenesis and virulence in the meningitis-causing pathogen Cryptococcus neoformans
Yixuan Jiang, Fujie Zhao, Ying Liang, Zhenguo Lu, Siyu Wang, Yao Meng, Zhanxiang Liu, Jing Zhang, Youbao Zhao
bioRxiv 2024.05.20.594937; doi: https://doi.org/10.1101/2024.05.20.594937

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