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Nat Commun. 2017 Nov 10;8(1):1428. doi: 10.1038/s41467-017-01425-3.

KSRP specifies monocytic and granulocytic differentiation through regulating miR-129 biogenesis and RUNX1 expression.

Author information

1
State Key Laboratory of Medical Molecular Biology, Department of Biochemistry & Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, 100005, China.
2
State Key Laboratory of Medical Molecular Biology, Department of Physiology and Pathophysiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, 100005, China.
3
Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, 401120, China.
4
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China.
5
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China. wangdong@ems.hrbmn.edu.cn.
6
Center for Informational Biology, University of Electronic Science and Technology of China, Chengdu, 610054, China. wangdong@ems.hrbmn.edu.cn.
7
State Key Laboratory of Medical Molecular Biology, Department of Biochemistry & Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, 100005, China. wo_wfang@hotmail.com.
8
State Key Laboratory of Medical Molecular Biology, Department of Biochemistry & Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, 100005, China. j-yu@ibms.pumc.edu.cn.

Abstract

RNA-binding proteins (RBPs) integrate the processing of RNAs into post-transcriptional gene regulation, but the direct contribution of them to myeloid cell specification is poorly understood. Here, we report the first global RBP transcriptomic analysis of myeloid differentiation by combining RNA-seq analysis with myeloid induction in CD34+ hematopoietic progenitor cells. The downregulated expression of the KH-Type Splicing Regulatory Protein (KSRP) during monocytopoiesis and up-regulated expression during granulopoiesis suggests that KSRP has divergent roles during monocytic and granulocytic differentiation. A further comparative analysis of miRNA transcripts reveals that KSRP promotes the biogenesis of miR-129, and the expression patterns and roles of miR-129 in myeloid differentiation are equivalent to those of KSRP. Finally, miR-129 directly blocks the expression of Runt Related Transcription Factor 1 (RUNX1), which evokes transcriptional modulation by RUNX1. Based on our findings, KSRP, miR-129, and RUNX1 participate in a regulatory axis to control the outcome of myeloid differentiation.

PMID:
29127290
PMCID:
PMC5681548
DOI:
10.1038/s41467-017-01425-3
[Indexed for MEDLINE]
Free PMC Article

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