science pharmaceutical expo biotech jobs
Originally published online as doi:10.1189/jlb.0907641 on January 24, 2008

Published online before print January 24, 2008
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jlb.0907641v1
83/4/982    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wang, S.
Right arrow Articles by Danner, R. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wang, S.
Right arrow Articles by Danner, R. L.
(Journal of Leukocyte Biology. 2008;83:982-990.)
© 2008 by Society for Leukocyte Biology

Nitric oxide-p38 MAPK signaling stabilizes mRNA through AU-rich element-dependent and -independent mechanisms

Shuibang Wang, Jianhua Zhang, Yi Zhang, Steven Kern and Robert L. Danner1

Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA

1 Correspondence: Critical Care Medicine Department, Bldg. 10, Rm. 2C145, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA. E-mail: rdanner{at}cc.nih.gov

Regulation of mRNA stability by p38 MAPK has been linked to adenosine-uridine-rich elements (AURE) within the 3'-untranslated region (3'UTR) of mRNA. Using microarrays, we previously found that AURE-containing mRNA is over-represented among transcripts up-regulated by NO•, an activator of p38 MAPK. Here, we investigated NO•-induced mRNA stabilization of specific AURE-containing genes to determine the sequence specificity and protein-binding interactions associated with this effect. IL-8, TNF-{alpha}, and p21/Waf1 3'UTRs were inserted into a luciferase (LUC) reporter gene system and found to decrease LUC activity and mRNA half-life in transfected THP-1 cells. The inhibitory effect of these 3'UTRs on LUC expression inversely correlated with the number of AUUUA motifs. Sequence truncation of the IL-8 3'UTR revealed that two segments, one with AURE sites and another without, contributed to mRNA destabilization. NO• activation of p38 MAPK increased LUC activity and mRNA half-life for reporter constructs that contained either of these IL-8 3'UTR segments. AURE-dependent and -independent NO• effects were blocked by p38 MAPK inhibition, and AURE-dependent effects were also blocked by site-directed mutagenesis of AUUUA sites. Two proteins, HuR and heterogeneous nuclear ribonucleoprotein A0, were identified, which bound to the AURE-containing region of exogenous and endogenous IL-8 mRNA in a NO•-p38 MAPK-dependent manner. These results demonstrate that NO•-p38 MAPK signaling can stabilize mRNA via AURE-dependent and -independent mechanisms.

Key Words: signal transduction • post-transcriptional gene regulation • HuR • hnRNP A0




This article has been cited by other articles:


Home page
 Am. J. Physiol. Cell Physiol.Home page
W. Hu, F. Li, S. Mahavadi, and K. S. Murthy
Upregulation of RGS4 expression by IL-1{beta} in colonic smooth muscle is enhanced by ERK1/2 and p38 MAPK and inhibited by the PI3K/Akt/GSK3{beta} pathway
Am J Physiol Cell Physiol, June 1, 2009; 296(6): C1310 - C1320.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
Y. Kuwano, A. Rabinovic, S. Srikantan, M. Gorospe, and B. Demple
Analysis of Nitric Oxide-Stabilized mRNAs in Human Fibroblasts Reveals HuR-Dependent Heme Oxygenase 1 Upregulation
Mol. Cell. Biol., May 15, 2009; 29(10): 2622 - 2635.
[Abstract] [Full Text] [PDF]