KHSRP combines transcriptional and posttranscriptional mechanisms to regulate monocytic differentiation. Issue 3 (1st July 2022)

• Record Type: Journal Article
• Authors: Xu, Jiayue; Wang, Dongsheng; Ma, Hongliu; Zhai, Xueying; Huo, Yue; Ren, Yue; Li, Weiqian; Chang, Le; Lu, Dongxu; Guo, Yuehong; Si, Yanmin; Gao, Yufeng; Wang, Xiaoshuang; Ma, Yanni; Wang, Fang; Yu, Jia
• Is Part Of: Blood science. Volume 4:Issue 3(2022)
• Page Start: 103
• Page End: 115
• Publication Date: 2022-07-01
• Subjects: KHSRP -- Monocytic differentiation -- RNA-binding proteins -- Transcriptional regulation; Hematology -- Periodicals; Blood -- Periodicals; Hematology; Blood; Hematology; Blood; Electronic journals; Periodicals; 616.15005
• DOI: 10.1097/BS9.0000000000000122
• Languages: English
• ISSNs: 2543-6368

Abstract

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.