We previously observed that nitric oxide (NO) exposure increases the stability 
of mRNAs encoding heme oxygenase 1 (HO-1) and TIEG-1 in human and mouse 
fibroblasts. Here, we have used microarrays to look broadly for changes in mRNA 
stability in response to NO treatment. Using human IMR-90 and mouse NIH 3T3 
fibroblasts treated with actinomycin D to block de novo transcription, 
microarray analysis suggested that the stability of the majority of mRNAs was 
unaffected. Among the mRNAs that were stabilized by NO treatment, seven 
transcripts were found in both IMR-90 and NIH 3T3 cells (CHIC2, GADD45B, HO-1, 
PTGS2, RGS2, TIEG, and ID3) and were chosen for further analysis. All seven 
mRNAs showed at least one hit of a signature motif for the stabilizing 
RNA-binding protein (RBP) HuR; accordingly, ribonucleoprotein 
immunoprecipitation analysis revealed that all seven mRNAs associated with HuR. 
In keeping with a functional role of HuR in the response to NO, a measurable 
fraction of HuR increased in the cytoplasm following NO treatment. However, 
among the seven transcripts, only HO-1 mRNA showed a robust increase in the 
level of its association with HuR following NO treatment. In turn, HO-1 mRNA and 
protein levels were significantly reduced when HuR levels were silenced in 
IMR-90 cells, and they were elevated when HuR was overexpressed. In sum, our 
results indicate that NO stabilizes mRNA subsets in fibroblasts, identify HuR as 
an RBP implicated in the NO response, reveal that HuR alone is insufficient for 
stabilizing several mRNAs by NO, and show that HO-1 induction by NO is regulated 
by HuR.