The yeast RNA methylation complex consists of conserved yet reconfigured components with m6A-dependent and independent roles

N6-methyladenosine (m6A), the most abundant mRNA modification, is deposited in mammals/drosophila/plants by m6A methyltransferase complexes (MTC) comprising a catalytic subunit and at least five additional proteins. The yeast MTC is critical for meiosis but was known to comprise three proteins, of which two were conserved in mammals. We uncover three novel MTC components (Kar4/Ygl036w-Vir1/Dyn2). All MTC subunits, except for Dyn2, are essential for m6A deposition and have corresponding mammalian orthologs. Nonetheless, the yeast MTC is arranged differently from its mammalian counterpart. The yeast MTC features a mostly mutually stabilizing core comprising Ime4/Mum2/Vir1 and the mRNA binding component Kar4, and an auxiliary hub comprising Slz1/Dyn2. The MTC core subunits when in a complex have both m6A-dependent and m6A-independent functions in meiosis. Kar4 also has a mechanistically separate function from the MTC during mating. Our findings expand the relevance of yeast as a model for unravelling m6A-dependent and independent functions of MTCs.N6-甲基腺嘌呤（N6-methyladenosine，m6A）是丰度最高的信使RNA（messenger RNA，mRNA）修饰形式，在哺乳动物、果蝇及植物中，该修饰的沉积由含有催化亚基与至少五种附加蛋白的m6A甲基转移酶复合物（m6A methyltransferase complexes，MTC）催化完成。酵母MTC对减数分裂过程至关重要，此前仅知其由三种蛋白组成，其中两种在哺乳动物中具有保守同源蛋白。本研究首次鉴定出三种全新的MTC组分（Kar4/Ygl036w-Vir1/Dyn2）。除Dyn2外，所有MTC亚基均为m6A修饰沉积所必需，且在哺乳动物中均存在对应的直系同源蛋白。尽管如此，酵母MTC的组装模式与其哺乳动物同源复合物存在显著差异。酵母MTC包含一个以相互稳定为核心特征的复合物结构，由Ime4/Mum2/Vir1与mRNA结合组分Kar4构成，同时还存在一个由Slz1/Dyn2组成的辅助枢纽。形成复合物的MTC核心亚基在减数分裂中同时具备m6A依赖型与非依赖型两种功能。Kar4在酵母交配过程中还拥有与MTC无关的独立作用机制。本研究结果拓展了酵母作为模型系统的应用价值，助力解析MTC的m6A依赖型与非依赖型功能。