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DOI	10.1073/pnas.2109668118
	Distinct roles of hnRNPH1 low-complexity domains in splicing and transcription
	Kim G.H.; Kwon I.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:50
英文摘要	Heterogeneous nuclear ribonucleoproteins (hnRNPs) represent a large family of RNA-binding proteins that control key events in RNA biogenesis under both normal and diseased cellular conditions. The low-complexity (LC) domain of hnRNPs can become liquid-like droplets or reversible amyloid-like polymers by phase separation. Yet, whether phase separation of the LC domains contributes to physiological functions of hnRNPs remains unclear. hnRNPH1 contains two LC domains, LC1 and LC2. Here, we show that reversible phase separation of the LC1 domain is critical for both interaction with different kinds of RNA-binding proteins and control of the alternative-splicing activity of hnRNPH1. Interestingly, although not required for phase separation, the LC2 domain contributes to the robust transcriptional activation of hnRNPH1 when fused to the DNA-binding domain, as found recently in acute lymphoblastic leukemia. Our data suggest that the ability of the LC1 domain to phase-separate into reversible polymers or liquid-like droplets is essential for function of hnRNPH1 as an alternative RNA-splicing regulator, whereas the LC2 domain may contribute to the aberrant transcriptional activity responsible for cancer transformation. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	HnRNPH1; Low-complexity domain; Phase separation; Splicing; Transcription
语种	英语
scopus关键词	DHX9 protein; heterogeneous nuclear ribonucleoprotein; heterogeneous nuclear ribonucleoprotein A1; heterogeneous nuclear ribonucleoprotein A2; heterogeneous nuclear ribonucleoprotein H1; RNA binding protein; RNA binding protein FUS; TAF15 protein; tyrosine; unclassified drug; antibody; heterogeneous nuclear ribonucleoprotein group F H; recombinant protein; alternative RNA splicing; amino terminal sequence; Article; binding assay; carboxy terminal sequence; confocal microscopy; controlled study; DNA binding domain; genetic transcription; human; human cell; hydrogel binding assay; immunoprecipitation; low complexity domain; phase separation; protein expression; protein protein interaction; protein structure; real time polymerase chain reaction; transcription initiation; Western blotting; gene expression regulation; genetics; HEK293 cell line; metabolism; molecular cloning; physiology; protein domain; RNA splicing; Antibodies; Cloning, Molecular; Gene Expression Regulation; HEK293 Cells; Heterogeneous-Nuclear Ribonucleoprotein Group F-H; Humans; Protein Domains; Recombinant Proteins; RNA Splicing
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/250934
作者单位	Department of Anatomy and Cell Biology, Sungkyunkwan University, School of Medicine, Suwon, 16419, South Korea
推荐引用方式 GB/T 7714	Kim G.H.,Kwon I.. Distinct roles of hnRNPH1 low-complexity domains in splicing and transcription[J],2021,118(50).
APA	Kim G.H.,&Kwon I..(2021).Distinct roles of hnRNPH1 low-complexity domains in splicing and transcription.Proceedings of the National Academy of Sciences of the United States of America,118(50).
MLA	Kim G.H.,et al."Distinct roles of hnRNPH1 low-complexity domains in splicing and transcription".Proceedings of the National Academy of Sciences of the United States of America 118.50(2021).