HuR posttranscriptionally regulates early growth response-1 (Egr-1) expression at the early stage of T cell activation

• Published in: FEBS letters Vol. 586; no. 24; pp. 4319 - 4325
• Main Authors: Mou, Zongchun, You, Jia, Xiao, Qianghai, Wei, Youheng, Yuan, Juan, Liu, Yong, Brewer, Gary, Ma, Wei-Jun
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 14.12.2012
• Subjects: 3' Untranslated Regions - physiology; 3′-untranslated region; 3′UTR; Act D; actinomycin D; ARE; ARE-binding proteins; ARE-BPs; AU-rich element; CHX; cycloheximide; Early Growth Response Protein 1 - biosynthesis; Early Growth Response Transcription Factors - metabolism; early growth response-1; Egr-1; ELAV Proteins - metabolism; Gene Expression Regulation; half-life; Humans; HuR; Jurkat Cells; Lymphocyte Activation; messenger ribonucleoprotein; mRNP; mRNP-immunoprecipitation; mRNP-IP; Posttranscriptional regulation; Ribonucleoproteins - metabolism; RNA Processing, Post-Transcriptional; RNA-Binding Proteins - metabolism; T cell activation; T-Lymphocytes - immunology; t1\2; Translation; Translation; HuR; T cell activation; 3′UTR; t1\2; ARE-BPs; Egr-1; mRNP-IP; Posttranscriptional regulation; CHX; ARE; Act D; mRNP
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2012.10.040

► Transiently expressed Egr-1 mRNA is identified in HuR mRNP complex. ► HuR regulates Egr-1 expression which in turn influences downstream IL-2 activation. ► HuR affects polyribosome distribution of Egr-1 mRNA and promotes translation. ► HuR controls translation of Egr-1 3′UTR reporter mRNA. ► Our study reveals a role for HuR in regulating early events of T cell activation. T cell activation depends on appropriate and precise regulation of gene expression. Here we find that rapidly translocated RNA-binding protein HuR, forms messenger ribonucleoprotein (mRNP) complexes with transiently expressed mRNAs encoding early-response transcription factors, including c-Fos, c-Jun, and Egr-1. Knockdown and overexpression assays demonstrated that proper posttranscriptional control of Egr-1 expression requires HuR-mediated translation control. Further analysis showed that the Egr-1 3′UTR, which contains AU-rich elements (AREs) and interacts directly with HuR, suppresses reporter gene expression and mediates posttranscriptional regulation of Egr-1 by HuR. These findings underscore an essential role for HuR in regulating early events during T cell activation.