Rtf1 HMD domain facilitates global histone H2B monoubiquitination and regulates morphogenesis and virulence in the meningitis-causing pathogen Cryptococcus neoformans
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 huma...
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eLife Sciences Publications Ltd
2025-05-01
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| Online Access: | https://elifesciences.org/articles/99229 |
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| author | Yixuan Jiang Ying Liang Fujie Zhao Zhenguo Lu Siyu Wang Yao Meng Zhanxiang Liu Jing Zhang Youbao Zhao |
| author_facet | Yixuan Jiang Ying Liang Fujie Zhao Zhenguo Lu Siyu Wang Yao Meng Zhanxiang Liu Jing Zhang Youbao Zhao |
| author_sort | Yixuan Jiang |
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| description | 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. |
| format | Article |
| id | doaj-art-cb788d2cc976463e81da8965e44bed24 |
| institution | OA Journals |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj-art-cb788d2cc976463e81da8965e44bed242025-08-20T02:15:18ZengeLife Sciences Publications LtdeLife2050-084X2025-05-011310.7554/eLife.99229Rtf1 HMD domain facilitates global histone H2B monoubiquitination and regulates morphogenesis and virulence in the meningitis-causing pathogen Cryptococcus neoformansYixuan Jiang0Ying Liang1Fujie Zhao2Zhenguo Lu3Siyu Wang4Yao Meng5Zhanxiang Liu6Jing Zhang7Youbao Zhao8https://orcid.org/0000-0003-2406-3922College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, ChinaCollege of Veterinary Medicine, Henan Agricultural University, Zhengzhou, ChinaCollege of Veterinary Medicine, Henan Agricultural University, Zhengzhou, ChinaCollege of Veterinary Medicine, Henan Agricultural University, Zhengzhou, ChinaCollege of Veterinary Medicine, Henan Agricultural University, Zhengzhou, ChinaCollege of Veterinary Medicine, Henan Agricultural University, Zhengzhou, ChinaCollege of Veterinary Medicine, Henan Agricultural University, Zhengzhou, ChinaCollege of Veterinary Medicine, Henan Agricultural University, Zhengzhou, ChinaCollege of Veterinary Medicine, Henan Agricultural University, Zhengzhou, China; Key Laboratory of Quality and Safety Control of Poultry Products, Ministry of Agriculture and Rural Affairs, Zhengzhou, China; Henan Province Key Laboratory of Animal Food Pathogens Surveillance, Zhengzhou, ChinaRtf1 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.https://elifesciences.org/articles/99229Rtf1histone modification domainH2B ubiquitinationCryptococcus neoformansyeast-to-hypha transitionvirulence |
| spellingShingle | Yixuan Jiang Ying Liang Fujie Zhao Zhenguo Lu Siyu Wang Yao Meng Zhanxiang Liu Jing Zhang Youbao Zhao Rtf1 HMD domain facilitates global histone H2B monoubiquitination and regulates morphogenesis and virulence in the meningitis-causing pathogen Cryptococcus neoformans eLife Rtf1 histone modification domain H2B ubiquitination Cryptococcus neoformans yeast-to-hypha transition virulence |
| title | Rtf1 HMD domain facilitates global histone H2B monoubiquitination and regulates morphogenesis and virulence in the meningitis-causing pathogen Cryptococcus neoformans |
| title_full | Rtf1 HMD domain facilitates global histone H2B monoubiquitination and regulates morphogenesis and virulence in the meningitis-causing pathogen Cryptococcus neoformans |
| title_fullStr | Rtf1 HMD domain facilitates global histone H2B monoubiquitination and regulates morphogenesis and virulence in the meningitis-causing pathogen Cryptococcus neoformans |
| title_full_unstemmed | Rtf1 HMD domain facilitates global histone H2B monoubiquitination and regulates morphogenesis and virulence in the meningitis-causing pathogen Cryptococcus neoformans |
| title_short | Rtf1 HMD domain facilitates global histone H2B monoubiquitination and regulates morphogenesis and virulence in the meningitis-causing pathogen Cryptococcus neoformans |
| title_sort | rtf1 hmd domain facilitates global histone h2b monoubiquitination and regulates morphogenesis and virulence in the meningitis causing pathogen cryptococcus neoformans |
| topic | Rtf1 histone modification domain H2B ubiquitination Cryptococcus neoformans yeast-to-hypha transition virulence |
| url | https://elifesciences.org/articles/99229 |
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