{"title":"KHSRP combines transcriptional and posttranscriptional mechanisms to regulate monocytic differentiation.","authors":"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","doi":"10.1097/BS9.0000000000000122","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":67343,"journal":{"name":"血液科学(英文)","volume":"4 3","pages":"103-115"},"PeriodicalIF":1.5000,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9742092/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"血液科学(英文)","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1097/BS9.0000000000000122","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"HEMATOLOGY","Score":null,"Total":0}
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.