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Nucleic Acids Research, 2000, Vol. 28, No. 14 2695-2701
© 2000 Oxford University Press

The identification of an endonuclease that cleaves within an HuR binding site in mRNA

Zhiquan Zhao, Feng-Ching Chang and Henry M. Furneaux*

Program in Molecular Pharmacology and Therapeutics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA

Messenger RNAs (mRNAs) that contain U-rich elements are targeted for rapid decay. Selective inhibition of this decay results in a rapid increase in steady state level. Thus, this is an important regulatory step in gene expression. Previously, we have found that these mRNAs are selectively stabilized by a specific mRNA binding protein called HuR. The mechanism of action of HuR is not well understood. It has been postulated that HuR stabilizes mRNA by the displacement or inhibition of factors that specifically cleave or deadenyl­ate these mRNAs. In this paper, we report the identification and characterization of a novel endo­nuclease that cleaves within an HuR binding site in p27kip1 mRNA. The specificity of this endonuclease and its inhibition by HuR argue for it playing a role in the postranscriptional regulation of gene expression.

* To whom correspondence should be addressed. Tel: +1 212 639 8701; Fax: +1 212 639 2861; Email: h-furneaux@ski.mskcc.org


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