The RNA-binding protein HuR stabilizes cytosolic phospholipase A 2α mRNA under Interleukin-1β treatment in non-small cell lung cancer A549 cells

Wan Lin Liao, Wei Chiao Wang, Wen Chang Chang, Joseph T. Tseng

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The activation of cytosolic phospholipase A 2α (cPLA 2α) plays an important role in initiating the inflammatory response. The regulation of cPLA 2α mRNA turnover has been proposed to control cPLA 2α gene expression under cytokine and growth factor stimulation. However, the detailed mechanism is still unknown. In this report, we have demonstrated that the cPLA 2α mRNA stability was increased under IL-1β treatment in A549 cells. By using EMSAs, HuR was identified as binding with the cPLA 2α mRNA 3′-UTR, and the binding region was located at nucleotides 2716-2807, a fragment containing AUUUA flanked by U-rich sequences. IL-1β treatment enhanced the association of cPLA 2α mRNA with cytosolic HuR. The reduction of HuR expression by RNA interference technology inhibited IL-1β-induced cPLA 2α mRNA and protein expression. Furthermore, blocking the p38 MAPK signaling pathway with SB203580 abolished the effect of IL-1β-induced cPLA 2α gene expression. Phosphorylation at residue Thr-118 of HuR is crucial in regulating the interaction between HuR and its target mRNAs. Mutation of HuR Thr-118 reduced the association between HuR and cPLA 2α mRNA under IL-1β treatment. This inhibitory effect was also observed in binding with COX-2 mRNA. This result indicated that p38 MAPK-mediated Thr-118 phosphorylation may play a key role in regulating the interaction of HuR with its target mRNAs in inflammation.

Original languageEnglish
Pages (from-to)35499-35508
Number of pages10
JournalJournal of Biological Chemistry
Volume286
Issue number41
DOIs
Publication statusPublished - Oct 14 2011

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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