Identification of HuR as a protein implicated in AUUUA-mediated mRNA decay.
Expression of many proto-oncogenes, cytokines and lymphokines is regulated by targeting their messenger RNAs for rapid degradation. Essential signals for this control are AU-rich elements (AREs) in the 3' untranslated region (UTR) of these messages. The ARE is loosely defined as the five-nucleotide sequence AUUUA embedded in a uracil-rich region. A transacting factor, presumably a protein, binds the ARE and initiates recognition by the destabilization machinery. Numerous candidate ARE-binding proteins have been proposed. We show that a 32 kDa protein in HeLa nuclear extracts characterized previously has RNA-binding specificity that correlates with the activity of an ARE in directing mRNA decay. Purification and subsequent analyses demonstrate that this 32 kDa protein is identical to a recently identified member of the Elav-like gene family (ELG) called HuR. The in vitro binding selectivity of HuR is indicative of an ARE sequence's ability to destabilize a mRNA in vivo, suggesting a critical role for HuR in the regulation of mRNA degradation.
Myer
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VE
Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520, USA.
Fan
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XC
Steitz
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JA
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D000954:Antigens, Surface; D001482:Base Composition; D002457:Cell Extracts; D003432:Cross-Linking Reagents; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D005786:Gene Expression Regulation / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D014466:Ultraviolet Rays
D000954:Antigens, Surface; D002457:Cell Extracts; D003432:Cross-Linking Reagents; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins