한빛사논문
S. Chul Kwon1,2,3,†, Harim Jang1,2,†, Siyuan Shen4,†, S. Chan Baek1,2, Kijun Kim1,2, Jihye Yang1,2, Jeesoo Kim1,2, Jong-Seo Kim1,2, Suman Wang4, Yunyu Shi4, Fudong Li4,* and V. Narry Kim1,2,*
1Center for RNA Research, Institute for Basic Science, Seoul 08826, Korea,
2School of Biological Sciences, Seoul National University, Seoul 08826, Korea,
3School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China and
4Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230026, China
*To whom correspondence should be addressed.
†The authors wish it to be known that, in their opinion, the first three authors should be regarded as Joint First Authors
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.
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