The methyltransferase complex (MTC) deposits N6-adenosine (m⁶A) 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 m⁶A levels. Reciprocally, MTC can recruit the microprocessor to the MIRNA loci, prompting co-transcriptional cleavage of primary miRNA substrates. Additionally, primary miRNA substrates carrying m⁶A modifications at their single-stranded basal regions are enriched by m⁶A 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 （m⁶A） 沉积到 RNA 上，而微处理器产生 microRNA。这两种不同的复合物是否以及如何相互交叉调节的研究很少。在这里，我们报道了 MTC 亚基 B 倾向于形成活性较差的不溶性缩合物，其水平由 20S 蛋白酶体监测。相反，微处理器组分 SERRATE （SE） 形成液体状缩合物，这反过来又促进了 MTC 亚基 B 的溶解度和稳定性，从而导致 MTC 活性增加。一致地，表达 SE 变体的亚态谱系在 MTC 相互作用或液体样相行为方面存在缺陷，表现出降低的 m⁶A 水平。反反地，MTC 可以将微处理器募集到 MIRNA 基因座，促进初级 miRNA 底物的共转录切割。此外，在其单链基底区域携带 m⁶A 修饰的初级 miRNA 底物被 m⁶A 读取器富集，该读取器将微处理器保留在核质中以进行持续加工。这揭示了通过 MTC 和微处理器配位在 RNA 修饰和加工中相分离的一种未被重视的机制。