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

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

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

Shuibang Wang,Jianhua Zhang,Yi Zhang,Steven Kern,Robert L Danner,

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.

Nitric oxide-p38 MAPK signaling stabilizes mRNA through AU-rich element-dependent and -independent mechanisms. Publishing Authors By Initials

S Wang,J Zhang,Y Zhang,S Kern,RL Danner,

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

PUBLICATION TYPE: Journal Article

Journal: Journal of leukocyte biology

VOLUME: 83

Page Numbers: 982-90

Journal Abbreviation: J. Leukoc. Biol.

ISSN: 0741-5400

DAY: 24

MONTH: 01

YEAR: 2008

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

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LANGUAGE: eng

NlmUniqueID: 8405628

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AFFILIATION: Bldg. 10, Rm. 2C145, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA. rdanner@cc.nih.gov.

Country: United States

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MEDLINETA: J Leukoc Biol

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