Identification of HuR as a protein implicated in AUUUA-mediated mRNA decay

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Abstract
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 trans‐acting 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 sequence9s ability to destabilize a mRNA in vivo, suggesting a critical role for HuR in the regulation of mRNA degradation.