Zhong Songxiao, Li Xindi, Li Changhao, Bai Haiyan, Chen Jingjing, Gan Lu, Zhu Jiyun, Oh Taerin, Yan Xingxing, Zhu Jiaying, Li Niankui, Koiwa Hisashi, Meek Thomas, Peng Xu, Yu Bin, Zhang Zhonghui, Zhang Xiuren
Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX, USA.
Guangdong Provincial Key Laboratory of Biotechnology for Plant Development, School of Life Science, South China Normal University, Guangzhou, China.
Nat Cell Biol. 2024 Dec;26(12):2129-2143. doi: 10.1038/s41556-024-01530-8. Epub 2024 Oct 29.
The methyltransferase complex (MTC) deposits N6-adenosine (mA) onto RNA, whereas the microprocessor produces microRNA. Whether and how these two distinct complexes cross-regulate each other has been poorly studied. Here we report that the MTC subunit B tends to form insoluble condensates with poor activity, with its level monitored by the 20S proteasome. Conversely, the microprocessor component SERRATE (SE) forms liquid-like condensates, which in turn promote the solubility and stability of the MTC subunit B, leading to increased MTC activity. Consistently, the hypomorphic lines expressing SE variants, defective in MTC interaction or liquid-like phase behaviour, exhibit reduced mA levels. Reciprocally, MTC can recruit the microprocessor to the MIRNA loci, prompting co-transcriptional cleavage of primary miRNA substrates. Additionally, primary miRNA substrates carrying mA modifications at their single-stranded basal regions are enriched by mA readers, which retain the microprocessor in the nucleoplasm for continuing processing. This reveals an unappreciated mechanism of phase separation in RNA modification and processing through MTC and microprocessor coordination.
甲基转移酶复合物（MTC）将N6-腺苷（mA）沉积到RNA上，而微处理器则产生微小RNA。这两种不同的复合物是否以及如何相互交叉调节，目前研究较少。在这里，我们报告MTC亚基B倾向于形成活性较差的不溶性凝聚物，其水平由20S蛋白酶体监测。相反，微处理器组件锯齿蛋白（SE）形成液状凝聚物，进而促进MTC亚基B的溶解性和稳定性，导致MTC活性增加。一致地，表达SE变体的亚等位基因系在MTC相互作用或液状相行为方面存在缺陷，其mA水平降低。相反，MTC可以将微处理器招募到微小RNA基因座，促使初级微小RNA底物的共转录切割。此外，在其单链基部区域携带mA修饰的初级微小RNA底物被mA读取器富集，这些读取器将微处理器保留在核质中以继续进行加工。这揭示了一种通过MTC和微处理器协调在RNA修饰和加工中未被重视的相分离机制。
