ERH promotes primary microRNA processing beyond cluster assistance

Harim Jang, Junyoung Park and V. Narry Kim ()
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Harim Jang: Institute for Basic Science
Junyoung Park: Institute for Basic Science
V. Narry Kim: Institute for Basic Science

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: Abstract 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.

Date: 2025
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DOI: 10.1038/s41467-025-63015-y

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