Jang Harim, Park Junyoung, Kim V Narry
Center for RNA Research, Institute for Basic Science, Seoul, Korea.
School of Biological Sciences, Seoul National University, Seoul, Korea.
Nat Commun. 2025 Aug 25;16(1):7913. doi: 10.1038/s41467-025-63015-y.
MicroRNA (miRNA) maturation is initiated by the Microprocessor complex, comprising DROSHA and DGCR8, that processes primary miRNAs (pri-miRNAs). Recent studies have identified ERH and SAFB2 as auxiliary factors that enhance the functionality of the Microprocessor. These factors are required for cluster assistance, where optimal pri-miRNAs facilitate the processing of adjacent suboptimal pri-miRNAs. However, the specific action mechanisms of ERH and SAFB2 have not yet been defined. In this study, we found that ERH broadly enhances the processing of pri-miRNAs regardless of their genomic contexts, affecting both stand-alone and clustered ones. Suboptimal hairpins are affected more prominently by ERH knockdown than efficiently processed hairpins. In contrast, SAFB2 specifically supports the processing of suboptimal pri-miRNA hairpins within clusters. This study reveals the distinct roles of ERH and SAFB2 in cluster assistance and presents a new model, in which SAFB2 facilitates the Microprocessor's transfer between hairpins, while ERH enables the efficient processing of suboptimal pri-miRNAs.
微小RNA（miRNA）的成熟由包含DROSHA和DGCR8的微处理器复合体启动，该复合体负责处理初级miRNA（pri-miRNA）。最近的研究已将ERH和SAFB2鉴定为增强微处理器功能的辅助因子。这些因子对于簇辅助是必需的，其中最佳pri-miRNA促进相邻次优pri-miRNA的加工。然而，ERH和SAFB2的具体作用机制尚未明确。在本研究中，我们发现ERH广泛增强pri-miRNA的加工，无论其基因组背景如何，对单独的和成簇的pri-miRNA均有影响。与有效加工的发夹相比，次优发夹受ERH敲低的影响更为显著。相比之下，SAFB2特异性支持簇内次优pri-miRNA发夹的加工。本研究揭示了ERH和SAFB2在簇辅助中的不同作用，并提出了一种新模型，其中SAFB2促进微处理器在发夹之间的转移，而ERH使次优pri-miRNA能够高效加工。
