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Molecular and Cellular Biology, August 2000, p. 5947-5959, Vol. 20, No. 16
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

A U-Rich Element in the 5' Untranslated Region Is Necessary for the Translation of p27 mRNA

S. Sean Millard,1,2 Anxo Vidal,2 Maurice Markus,1,2 and Andrew Koff1,2,*

Graduate Program in Cell Biology and Genetics, Weill Graduate School of Medical Sciences, Cornell University,1 and Program in Molecular Biology, Memorial Sloan-Kettering Cancer Center,2 New York, New York 10021

Received 31 March 2000/Returned for modification 4 May 2000/Accepted 18 May 2000

Increased translation of p27 mRNA correlates with withdrawal of cells from the cell cycle. This raised the possibility that antimitogenic signals might mediate their effects on p27 expression by altering complexes that formed on p27 mRNA, regulating its translation. In this report, we identify a U-rich sequence in the 5' untranslated region (5'UTR) of p27 mRNA that is necessary for efficient translation in proliferating and nonproliferating cells. We show that a number of factors bind to the 5'UTR in vitro in a manner dependent on the U-rich element, and their availability in the cytosol is controlled in a growth- and cell cycle-dependent fashion. One of these factors is HuR, a protein previously implicated in mRNA stability, transport, and translation. Another is hnRNP C1 and C2, proteins implicated in mRNA processing and the translation of a specific subset of mRNAs expressed in differentiated cells. In lovastatin-treated MDA468 cells, the mobility of the associated hnRNP C1 and C2 proteins changed, and this correlated with increased p27 expression. Together, these data suggest that the U-rich dependent RNP complex on the 5'UTR may regulate the translation of p27 mRNA and may be a target of antimitogenic signals.

* Corresponding author. Mailing address: RRL917D, Box 207, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021. Phone: (212) 639-2354. Fax: (212) 639-2861. E-mail: a-koff{at}ski.mskcc.org.

Molecular and Cellular Biology, August 2000, p. 5947-5959, Vol. 20, No. 16
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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