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

Zongchun Mou; Jia You; Qianghai Xiao; Youheng Wei; Juan Yuan; Yong Liu; Gary Brewer; Wei Jun Ma

doi:10.1016/j.febslet.2012.10.040

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

Zongchun Mou, Jia You, Qianghai Xiao, Youheng Wei, Juan Yuan, Yong Liu, Gary Brewer, Wei Jun Ma

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	4319-4325
Number of pages	7
Journal	FEBS Letters
Volume	586
Issue number	24
DOIs	https://doi.org/10.1016/j.febslet.2012.10.040
State	Published - Dec 14 2012
Externally published	Yes

All Science Journal Classification (ASJC) codes

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

Keywords

3′UTR
Egr-1
HuR
Posttranscriptional regulation
T cell activation
Translation

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

abstract = "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.",

keywords = "3′UTR, Egr-1, HuR, Posttranscriptional regulation, T cell activation, Translation",

author = "Zongchun Mou and Jia You and Qianghai Xiao and Youheng Wei and Juan Yuan and Yong Liu and Gary Brewer and Ma, {Wei Jun}",

note = "Funding Information: We thank Dr. Nan Shen and Dr. Yuanjia Tang for facilitating nucleofection experiments, and we thank Dr. Qing Jing for technical assistance of polyribosome profile analysis. We are grateful to Dr. Huangtian Yang and Dr. Xiaojia Chen for providing plasmids. This work was supported by grants from the National Natural Science Foundation of China (Grant No. 30570390 , No. 30470381 ), the Knowledge Innovation Program of the Chinese Academy of Sciences (Grant No. KSCX2-YW-R-175 ), and a Chinese Academy of Sciences Visiting Professorship for Senior International Scientists (Grant No. 2009S1-22 ). G.B. was supported by NIH grant R01 CA052443 and a Visiting Professorship at the Institute of Health Sciences, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences. This work was also supported in part by the Shanghai Commission of Science and Technology. ",

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doi = "10.1016/j.febslet.2012.10.040",

language = "English (US)",

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T1 - HuR posttranscriptionally regulates early growth response-1 (Egr-1) expression at the early stage of T cell activation

AU - Mou, Zongchun

AU - You, Jia

AU - Xiao, Qianghai

AU - Wei, Youheng

AU - Yuan, Juan

AU - Liu, Yong

AU - Brewer, Gary

AU - Ma, Wei Jun

N1 - Funding Information: We thank Dr. Nan Shen and Dr. Yuanjia Tang for facilitating nucleofection experiments, and we thank Dr. Qing Jing for technical assistance of polyribosome profile analysis. We are grateful to Dr. Huangtian Yang and Dr. Xiaojia Chen for providing plasmids. This work was supported by grants from the National Natural Science Foundation of China (Grant No. 30570390 , No. 30470381 ), the Knowledge Innovation Program of the Chinese Academy of Sciences (Grant No. KSCX2-YW-R-175 ), and a Chinese Academy of Sciences Visiting Professorship for Senior International Scientists (Grant No. 2009S1-22 ). G.B. was supported by NIH grant R01 CA052443 and a Visiting Professorship at the Institute of Health Sciences, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences. This work was also supported in part by the Shanghai Commission of Science and Technology.

PY - 2012/12/14

Y1 - 2012/12/14

N2 - 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.

AB - 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.

KW - 3′UTR

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KW - HuR

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KW - T cell activation

KW - Translation

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ER -

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

Abstract

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Keywords

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