Jiang Yixuan, Liang Ying, Zhao Fujie, Lu Zhenguo, Wang Siyu, Meng Yao, Liu Zhanxiang, Zhang Jing, Zhao Youbao
College 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.
Elife. 2025 May 12;13:RP99229. doi: 10.7554/eLife.99229.
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 , 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 . 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 Δ 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 .
Rtf1通常被认为是Paf1复合物（Paf1C）的一个亚基，Paf1C是一种多功能蛋白复合物，在多个阶段参与组蛋白修饰和RNA生物合成。Rtf1在[具体物种]中与Paf1C稳定结合，但在包括人类在内的其他物种中则不然。关于它在人类真菌病原体中的功能知之甚少。在这里，我们表明Rtf1是促进H2B单泛素化（H2Bub1）所必需的，并调节引起脑膜炎的真菌病原体中的真菌形态发生和致病性。Rtf1与Paf1C的结合并不紧密，其组蛋白修饰结构域（HMD）足以促进H2Bub1以及与真菌交配和丝状化相关基因的表达。此外，Rtf1 HMD完全恢复了真菌的形态发生和致病性；然而，在Δ菌株背景下，它未能恢复耐热性和黑色素产生的缺陷。本研究确立了隐球菌Rtf1作为一种不依赖Paf1C的调节因子在调节真菌形态发生和致病性中的作用，并突出了HMD在促进[具体物种]中全局H2Bub1方面的功能。
