Open AccessAU-Rich-Element-Dependent Translation Repression Requires the Cooperation of Tristetraprolin and RCK/P54
Author(s) -
Mei Yan Qi,
Zhi Zhang Wang,
Zhuo Zhang,
Qing Shao,
An Zeng,
Xiang Qi Li,
Wen Qing Li,
Chen Wang,
FuJu Tian,
Qing Li,
Jun Zou,
Yong Qin,
Gary Brewer,
Shuang Huang,
Qing Jing
Publication year - 2012
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.05340-11
Subject(s) - tristetraprolin , translation (biology) , gene knockdown , untranslated region , biology , messenger rna , repressor , translational regulation , psychological repression , three prime untranslated region , eukaryotic translation , microbiology and biotechnology , au rich element , luciferase , polysome , five prime untranslated region , protein biosynthesis , transfection , rna , biochemistry , genetics , gene expression , cell culture , ribosome , gene
AU-rich elements (AREs), residing in the 3′ untranslated region (UTR) of many labile mRNAs, are importantcis -acting elements that modulate the stability of these mRNAs by collaborating withtrans -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.