KHSRP combines transcriptional and posttranscriptional mechanisms to regulate monocytic differentiation.

IF 1.5 Q3 HEMATOLOGY
Jiayue Xu, Dongsheng Wang, Hongliu Ma, Xueying Zhai, Yue Huo, Yue Ren, Weiqian Li, Le Chang, Dongxu Lu, Yuehong Guo, Yanmin Si, Yufeng Gao, Xiaoshuang Wang, Yanni Ma, Fang Wang, Jia Yu
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引用次数: 0

Abstract

RNA-binding proteins (RBPs) are widely involved in the transcriptional and posttranscriptional regulation of multiple biological processes. The transcriptional regulatory ability of RBPs was indicated by the identification of chromatin-enriched RBPs (Che-RBPs). One of these proteins, KH-type splicing regulatory protein (KHSRP), is a multifunctional RBP that has been implicated in mRNA decay, alternative splicing, and miRNA biogenesis and plays an essential role in myeloid differentiation by facilitating the maturation of miR-129. In this study, we revealed that KHSRP regulates monocytic differentiation by regulating gene transcription and RNA splicing. KHSRP-occupied specific genomic sites in promoter and enhancer regions to regulate the expression of several hematopoietic genes through transcriptional activation and bound to pre-mRNA intronic regions to modulate alternative splicing during monocytic differentiation. Of note, KHSRP had co-regulatory effects at both the transcriptional and posttranscriptional levels on MOGOH and ADARB1. Taken together, our analyses revealed the dual DNA- and RNA-binding activities of KHSRP and have provided a paradigm to guide the analysis of other functional Che-RBPs in different biological systems.

Abstract Image

Abstract Image

Abstract Image

KHSRP结合转录和转录后机制调节单核细胞分化。
rna结合蛋白(rbp)广泛参与多种生物过程的转录和转录后调控。通过鉴定染色质富集的rbp (che - rbp)来表明rbp的转录调控能力。其中一种蛋白kh型剪接调节蛋白(KHSRP)是一种多功能RBP,与mRNA衰变、选择性剪接和miRNA生物发生有关,并通过促进miR-129的成熟在髓细胞分化中发挥重要作用。在本研究中,我们发现KHSRP通过调控基因转录和RNA剪接来调控单核细胞的分化。khsrp占据启动子和增强子区域的特定基因组位点,通过转录激活来调节几种造血基因的表达,并与mrna前内含子区域结合,在单核细胞分化过程中调节选择性剪接。值得注意的是,KHSRP在转录和转录后水平上对MOGOH和ADARB1具有共同调控作用。总之,我们的分析揭示了KHSRP的双重DNA和rna结合活性,并为不同生物系统中其他功能che - rbp的分析提供了一个范例。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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CiteScore
1.70
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