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

This SuperSeries is composed of the SubSeries listed below. Abstract: N6-methyladenosine (m6A), the most abundant mRNA modification, is deposited in mammals/insects/plants by m6A methyltransferase complexes (MTC) comprising a catalytic subunit and at least five additional proteins. The yeast MTC is critical for meiosis and was known to comprise three proteins, of which two were conserved. 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 MTC orthologs. Unlike the mammalian bipartite MTC, the yeast MTC is unipartite, yet multifunctional. The mRNA interacting module, comprising Ime4, Mum2, Vir1, and Kar4, exerts the MTC m6A-independent function, while Slz1 enables the MTC catalytic function in m6A deposition. Both functions are critical for meiotic progression. Kar4 also has a mechanistically separate role from the MTC during mating. The yeast MTC constituents play distinguishable m6A-dependent, MTC-dependent and MTC-independent functions, highlighting their complexity and paving the path towards dissecting multi-layered MTC functions in mammals.本超级数据集（SuperSeries）由下述子数据集（SubSeries）组成。 摘要：N6-甲基腺嘌呤（N6-methyladenosine，m6A）是信使RNA（mRNA）中最为丰富的修饰类型，在哺乳动物、昆虫与植物中，该修饰由N6-甲基腺嘌呤甲基转移酶复合物（m6A methyltransferase complexes，MTC）催化沉积，该复合物包含1个催化亚基与至少5种辅助蛋白。酵母MTC对减数分裂至关重要，此前已知其仅由3种蛋白组成，其中2种在进化中具有保守性。本研究发现了3种全新的MTC组分：Kar4/Ygl036w-Vir1/Dyn2。除Dyn2外，所有MTC亚基均对m6A修饰沉积不可或缺，且均存在对应的哺乳动物MTC同源蛋白。与哺乳动物的二分体MTC不同，酵母MTC为单一组分型复合物，却具备多重功能。由Ime4、Mum2、Vir1与Kar4组成的mRNA互作模块，可执行MTC不依赖m6A的功能；而Slz1则赋予MTC在m6A修饰沉积中的催化活性。上述两种功能均对减数分裂进程至关重要。Kar4在交配过程中还具备与MTC机制相互独立的独特功能。酵母MTC各组分分别承担依赖m6A、依赖MTC以及不依赖MTC的不同功能，这凸显了该复合物的功能复杂性，并为解析哺乳动物MTC的多层级功能铺平了研究道路。