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

58 Scopus citations

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 2012

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'AU-rich-element-dependent translation repression requires the cooperation of tristetraprolin and RCK/P54'. Together they form a unique fingerprint.

  • Cite this

    Qi, M. Y., Wang, Z. Z., Zhang, Z., Shao, Q., Zeng, A., Li, X. Q., Li, W. Q., Wang, C., Tian, F. J., Li, Q., Zou, J., Qin, Y. W., 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, 32(5), 913-928. https://doi.org/10.1128/MCB.05340-11