An important paradigm for post-transcriptional regulation is the control of 
cytoplasmic mRNA stability mediated by AU-rich elements (AREs) in the 3' 
untranslated region of transcripts encoding oncoproteins, cytokines and 
transcription factors. While many RNA-binding proteins have been shown to bind 
to AREs in vitro, neither the functional consequences nor the physiological 
significance of their interactions are known. Here we demonstrate a role for the 
embryonic lethal abnormal visual (ELAV) RNA-binding protein HuR in mRNA turnover 
in vivo. The ELAV family of RNA-binding proteins is highly conserved in 
vertebrates. In humans, there are four members; HuR is expressed in all 
proliferating cells, whereas Hel-N1, HuC and HuD are expressed in terminally 
differentiated neurons. We show that elevation of cytoplasmic HuR levels 
inhibits c-fos ARE-mediated RNA decay but has little effect on rapid decay 
directed by c-jun ARE. It appears that HuR has little effect on deadenylation 
but delays onset of decay of the RNA body and slows down its subsequent decay. 
We also show that HuR can be induced to redistribute from the nucleus to the 
cytoplasm and that this redistribution is associated with an altered function. 
Modulation of the ARE-mediated decay pathway through controlling distribution of 
the ELAV proteins between nucleus and cytoplasm may be a mechanism by which cell 
growth and differentiation is regulated.