[HTML][HTML] RNA stabilization by the AU‐rich element binding protein, HuR, an ELAV protein

SSY Peng, CYA Chen, N Xu, AB Shyu - The EMBO journal, 1998 - embopress.org
SSY Peng, CYA Chen, N Xu, AB Shyu
The EMBO journal, 1998embopress.org
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 …
Abstract
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.
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