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KHSRP combines transcriptional and posttranscriptional mechanisms to regulate monocytic differentiation.

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.

SUBMITTER: Xu J

PROVIDER: S-EPMC9742092 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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KHSRP combines transcriptional and posttranscriptional mechanisms to regulate monocytic differentiation.

Xu Jiayue J Wang Dongsheng D Ma Hongliu H Zhai Xueying X Huo Yue Y Ren Yue Y Li Weiqian W Chang Le L Lu Dongxu D Guo Yuehong Y Si Yanmin Y Gao Yufeng Y Wang Xiaoshuang X Ma Yanni Y Wang Fang F Yu Jia J

Blood science (Baltimore, Md.) 20220701 3

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 faci ...[more]

PMID: 36518592

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KHSRP combines transcriptional and posttranscriptional mechanisms to regulate monocytic differentiation.

Publications

KHSRP combines transcriptional and posttranscriptional mechanisms to regulate monocytic differentiation.

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