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

KSRP specifies monocytic and granulocytic differentiation through regulating miR-129 biogenesis and RUNX1 expression.
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KSRP 通过调节 miR-129 生物合成和 RUNX1 表达来指定单核细胞和粒细胞分化

DOI:
10.1038/s41467-017-01425-3
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发表时间:
2017-11-10
影响因子:
16.6
通讯作者:
Yu J
Yu J
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Zhao H;Wang X;Yi P;Si Y;Tan P;He J;Yu S;Ren Y;Ma Y;Zhang J;Wang D;Wang F;Yu J

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RNA结合蛋白(RBP)将RNA的加工整合到转录后基因调控中,但它们对骨髓细胞特化的直接贡献知之甚少。在这里,我们报告了通过将RNA-seq分析与CD 34+造血祖细胞中的髓样诱导相结合来进行髓样分化的第一个全局RBP转录组学分析。KH型剪接调节蛋白(KSRP)在单核细胞生成过程中的下调表达和在粒细胞生成过程中的上调表达表明KSRP在单核细胞和粒细胞分化过程中具有不同的作用。对miRNA转录本的进一步比较分析表明,KSRP促进了miR-129的生物合成,miR-129在髓系分化中的表达模式和作用与KSRP相当。最后,miR-129直接阻断Runt相关转录因子1(RUNX 1)的表达,RUNX 1引起RUNX 1的转录调节。基于我们的研究结果,KSRP、miR-129和RUNX 1参与调控轴以控制髓样分化的结果。
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.
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