ERH facilitates microRNA maturation through the interaction with the N-terminus of DGCR8

• Published in: Nucleic acids research 2020-11, Vol.48 (19), p.11097-11112
• Main Authors: Kwon, S Chul, Jang, Harim, Shen, Siyuan, Baek, S Chan, Kim, Kijun, Yang, Jihye, Kim, Jeesoo, Kim, Jong-Seo, Wang, Suman, Shi, Yunyu, Li, Fudong, Kim, V Narry
• Format: Article
• Language: English
• Subjects: Cell Cycle Proteins - metabolism; HCT116 Cells; HEK293 Cells; Humans; K562 Cells; MicroRNAs - metabolism; Protein Binding; Protein Conformation; RNA and RNA-protein complexes; RNA Processing, Post-Transcriptional; RNA-Binding Proteins - metabolism; Transcription Factors - metabolism
• ISSN: 0305-1048; 1362-4962; 1362-4962
• DOI: 10.1093/nar/gkaa827

Abstract The microprocessor complex cleaves the primary transcript of microRNA (pri-miRNA) to initiate miRNA maturation. Microprocessor is known to consist of RNase III DROSHA and dsRNA-binding DGCR8. Here, we identify Enhancer of Rudimentary Homolog (ERH) as a new component of Microprocessor. Through a crystal structure and biochemical experiments, we reveal that ERH uses its hydrophobic groove to bind to a conserved region in the N-terminus of DGCR8, in a 2:2 stoichiometry. Knock-down of ERH or deletion of the DGCR8 N-terminus results in a reduced processing of suboptimal pri-miRNAs in polycistronic miRNA clusters. ERH increases the processing of suboptimal pri-miR-451 in a manner dependent on its neighboring pri-miR-144. Thus, the ERH dimer may mediate ‘cluster assistance’ in which Microprocessor is loaded onto a poor substrate with help from a high-affinity substrate in the same cluster. Our study reveals a role of ERH in the miRNA biogenesis pathway.