RNA stabilization by the AU-rich element binding protein, HuR, an ELAV protein.
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.
Peng
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SS
Department of Biochemistry and Molecular Biology, University of Texas Houston Health Science Center Medical School, Houston, TX 77030, USA.
Chen
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CY
Xu
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Shyu
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D016475:3T3 Cells; D000818:Animals; D000954:Antigens, Surface; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D016762:Genes, fos / Q000502:physiology; D016758:Genes, jun / Q000502:physiology; D006801:Humans; D051379:Mice; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000378:metabolism*
D000954:Antigens, Surface; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins