Volume 27, No 3, Mar 2017

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 27 Issue 3, March 2017: 416-439

ORIGINAL ARTICLES

The RNA-binding protein QKI5 regulates primary miR-124-1 processing via a distal RNA motif during erythropoiesis

Fang Wang^1,*, Wei Song^1,*, Hongmei Zhao^1,*, Yanni Ma¹, Yuxia Li¹, Di Zhai¹, Jingnan Pi¹, Yanmin Si¹, Jiayue Xu¹, Lei Dong¹, Rui Su¹, Mengmeng Zhang¹, Yong Zhu¹, Xiaoxia Ren¹, Fei Miao¹, Wenjie Liu¹, Feng Li¹, Junwu Zhang¹, Aibin He², Ge Shan³, Jingyi Hui⁴, Linfang Wang¹ and Jia Yu¹

¹State Key Laboratory of Medical Molecular Biology, Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing 100005, China
²Institute of Molecular Medicine, Peking University, Beijing 100871, China
³School of Life Sciences, University of Sciences and Technology of China, Hefei, Anhui 230027, China
⁴State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China Correspondence: (j-yu@ibms.pumc.edu.cn)

MicroRNA (miRNA) biogenesis is finely controlled by complex layers of post-transcriptional regulators, including RNA-binding proteins (RBPs). Here, we show that an RBP, QKI5, activates the processing of primary miR-124-1 (pri-124-1) during erythropoiesis. QKI5 recognizes a distal QKI response element and recruits Microprocessor through interaction with DGCR8. Furthermore, the recruited Microprocessor is brought to pri-124-1 stem loops by a spatial RNA-RNA interaction between two complementary sequences. Thus, mutations disrupting their base-pairing affect the strength of QKI5 activation. When erythropoiesis proceeds, the concomitant decrease of QKI5 releases Microprocessor from pri-124-1 and reduces mature miR-124 levels to facilitate erythrocyte maturation. Mechanistically, miR-124 targets TAL1 and c-MYB, two transcription factors involved in normal erythropoiesis. Importantly, this QKI5-mediated regulation also gives rise to a unique miRNA signature, which is required for erythroid differentiation. Taken together, these results demonstrate the pivotal role of QKI5 in primary miRNA processing during erythropoiesis and provide new insights into how a distal element on primary transcripts affects miRNA biogenesis.

10.1038/cr.2017.26

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