AU-rich-element-dependent translation repression requires the cooperation of tristetraprolin and RCK/P54

Mei Yan Qi, Zhi Zhang Wang, Zhuo Zhang, Qin Shao, An Zeng, Xiang Qi Li, Wen Qing Li, Chen Wang, Fu Ju Tian, Qing Li, Jun Zou, Yong Wen Qin, Gary Brewer, Shuang Huang, Qing Jing

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

AU-rich elements (AREs), residing in the 3' untranslated region (UTR) of many labile mRNAs, are important cis-acting elements that modulate the stability of these mRNAs by collaborating with trans-acting factors such as tristetraprolin (TTP). AREs also regulate translation, but the underlying mechanism is not fully understood. Here we examined the function and mechanism of TTP in ARE-mRNA translation. Through a luciferase-based reporter system, we used knockdown, overexpression, and tethering assays in 293T cells to demonstrate that TTP represses ARE reporter mRNA translation. Polyribosome fractionation experiments showed that TTP shifts target mRNAs to lighter fractions. In murine RAW264.7 macrophages, knocking down TTP produces significantly more tumor necrosis factor alpha (TNF-α) than the control, while the corresponding mRNA level has a marginal change. Furthermore, knockdown of TTP increases the rate of biosynthesis of TNF-α, suggesting that TTP can exert effects at translational levels. Finally, we demonstrate that the general translational repressor RCK may cooperate with TTP to regulate ARE-mRNA translation. Collectively, our studies reveal a novel function of TTP in repressing ARE-mRNA translation and that RCK is a functional partner of TTP in promoting TTP-mediated translational repression.

Original languageEnglish (US)
Pages (from-to)913-928
Number of pages16
JournalMolecular and Cellular Biology
Volume32
Issue number5
DOIs
StatePublished - Mar 1 2012

Fingerprint

Tristetraprolin
AU Rich Elements
Protein Biosynthesis
Messenger RNA
Tumor Necrosis Factor-alpha
Trans-Activators
Polyribosomes
HEK293 Cells
RNA Stability
3' Untranslated Regions
Luciferases

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

AU-rich-element-dependent translation repression requires the cooperation of tristetraprolin and RCK/P54. / Qi, Mei Yan; Wang, Zhi Zhang; Zhang, Zhuo; Shao, Qin; Zeng, An; Li, Xiang Qi; Li, Wen Qing; Wang, Chen; Tian, Fu Ju; Li, Qing; Zou, Jun; Qin, Yong Wen; Brewer, Gary; Huang, Shuang; Jing, Qing.

In: Molecular and Cellular Biology, Vol. 32, No. 5, 01.03.2012, p. 913-928.

Research output: Contribution to journalArticle

Qi, MY, Wang, ZZ, Zhang, Z, Shao, Q, Zeng, A, Li, XQ, Li, WQ, Wang, C, Tian, FJ, Li, Q, Zou, J, Qin, YW, Brewer, G, Huang, S & Jing, Q 2012, 'AU-rich-element-dependent translation repression requires the cooperation of tristetraprolin and RCK/P54', Molecular and Cellular Biology, vol. 32, no. 5, pp. 913-928. https://doi.org/10.1128/MCB.05340-11
Qi, Mei Yan ; Wang, Zhi Zhang ; Zhang, Zhuo ; Shao, Qin ; Zeng, An ; Li, Xiang Qi ; Li, Wen Qing ; Wang, Chen ; Tian, Fu Ju ; Li, Qing ; Zou, Jun ; Qin, Yong Wen ; Brewer, Gary ; Huang, Shuang ; Jing, Qing. / AU-rich-element-dependent translation repression requires the cooperation of tristetraprolin and RCK/P54. In: Molecular and Cellular Biology. 2012 ; Vol. 32, No. 5. pp. 913-928.
@article{f1c8f54d0abc471fbb6c7dbc66ff97da,
title = "AU-rich-element-dependent translation repression requires the cooperation of tristetraprolin and RCK/P54",
abstract = "AU-rich elements (AREs), residing in the 3' untranslated region (UTR) of many labile mRNAs, are important cis-acting elements that modulate the stability of these mRNAs by collaborating with trans-acting factors such as tristetraprolin (TTP). AREs also regulate translation, but the underlying mechanism is not fully understood. Here we examined the function and mechanism of TTP in ARE-mRNA translation. Through a luciferase-based reporter system, we used knockdown, overexpression, and tethering assays in 293T cells to demonstrate that TTP represses ARE reporter mRNA translation. Polyribosome fractionation experiments showed that TTP shifts target mRNAs to lighter fractions. In murine RAW264.7 macrophages, knocking down TTP produces significantly more tumor necrosis factor alpha (TNF-α) than the control, while the corresponding mRNA level has a marginal change. Furthermore, knockdown of TTP increases the rate of biosynthesis of TNF-α, suggesting that TTP can exert effects at translational levels. Finally, we demonstrate that the general translational repressor RCK may cooperate with TTP to regulate ARE-mRNA translation. Collectively, our studies reveal a novel function of TTP in repressing ARE-mRNA translation and that RCK is a functional partner of TTP in promoting TTP-mediated translational repression.",
author = "Qi, {Mei Yan} and Wang, {Zhi Zhang} and Zhuo Zhang and Qin Shao and An Zeng and Li, {Xiang Qi} and Li, {Wen Qing} and Chen Wang and Tian, {Fu Ju} and Qing Li and Jun Zou and Qin, {Yong Wen} and Gary Brewer and Shuang Huang and Qing Jing",
year = "2012",
month = "3",
day = "1",
doi = "10.1128/MCB.05340-11",
language = "English (US)",
volume = "32",
pages = "913--928",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "5",

}

TY - JOUR

T1 - AU-rich-element-dependent translation repression requires the cooperation of tristetraprolin and RCK/P54

AU - Qi, Mei Yan

AU - Wang, Zhi Zhang

AU - Zhang, Zhuo

AU - Shao, Qin

AU - Zeng, An

AU - Li, Xiang Qi

AU - Li, Wen Qing

AU - Wang, Chen

AU - Tian, Fu Ju

AU - Li, Qing

AU - Zou, Jun

AU - Qin, Yong Wen

AU - Brewer, Gary

AU - Huang, Shuang

AU - Jing, Qing

PY - 2012/3/1

Y1 - 2012/3/1

N2 - AU-rich elements (AREs), residing in the 3' untranslated region (UTR) of many labile mRNAs, are important cis-acting elements that modulate the stability of these mRNAs by collaborating with trans-acting factors such as tristetraprolin (TTP). AREs also regulate translation, but the underlying mechanism is not fully understood. Here we examined the function and mechanism of TTP in ARE-mRNA translation. Through a luciferase-based reporter system, we used knockdown, overexpression, and tethering assays in 293T cells to demonstrate that TTP represses ARE reporter mRNA translation. Polyribosome fractionation experiments showed that TTP shifts target mRNAs to lighter fractions. In murine RAW264.7 macrophages, knocking down TTP produces significantly more tumor necrosis factor alpha (TNF-α) than the control, while the corresponding mRNA level has a marginal change. Furthermore, knockdown of TTP increases the rate of biosynthesis of TNF-α, suggesting that TTP can exert effects at translational levels. Finally, we demonstrate that the general translational repressor RCK may cooperate with TTP to regulate ARE-mRNA translation. Collectively, our studies reveal a novel function of TTP in repressing ARE-mRNA translation and that RCK is a functional partner of TTP in promoting TTP-mediated translational repression.

AB - AU-rich elements (AREs), residing in the 3' untranslated region (UTR) of many labile mRNAs, are important cis-acting elements that modulate the stability of these mRNAs by collaborating with trans-acting factors such as tristetraprolin (TTP). AREs also regulate translation, but the underlying mechanism is not fully understood. Here we examined the function and mechanism of TTP in ARE-mRNA translation. Through a luciferase-based reporter system, we used knockdown, overexpression, and tethering assays in 293T cells to demonstrate that TTP represses ARE reporter mRNA translation. Polyribosome fractionation experiments showed that TTP shifts target mRNAs to lighter fractions. In murine RAW264.7 macrophages, knocking down TTP produces significantly more tumor necrosis factor alpha (TNF-α) than the control, while the corresponding mRNA level has a marginal change. Furthermore, knockdown of TTP increases the rate of biosynthesis of TNF-α, suggesting that TTP can exert effects at translational levels. Finally, we demonstrate that the general translational repressor RCK may cooperate with TTP to regulate ARE-mRNA translation. Collectively, our studies reveal a novel function of TTP in repressing ARE-mRNA translation and that RCK is a functional partner of TTP in promoting TTP-mediated translational repression.

UR - http://www.scopus.com/inward/record.url?scp=84863116439&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84863116439&partnerID=8YFLogxK

U2 - 10.1128/MCB.05340-11

DO - 10.1128/MCB.05340-11

M3 - Article

C2 - 22203041

AN - SCOPUS:84863116439

VL - 32

SP - 913

EP - 928

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 5

ER -