A U-rich element in the 5 ' untranslated region is necessary for the translation of p27 mRNA

Increased translation of p27 mRNA correlates with withdrawal of cells from the cell cycle. This raised the possibility that antimitogenic signals migh t mediate their effects on p27 expression by altering complexes that formed on p27 mRNA, regulating its translation. In this report, we identify a U-r ich sequence in the 5' untranslated region (5'UTR) of p27 mRNA that is nece ssary 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 d ependent on the U-rich element, and their availability in the cytosol is co ntrolled in a growth- and cell cycle-dependent fashion. One of these factor s is HuR, a protein previously implicated in mRNA stability, transport, and translation. Another is hnRNP C1 and C2, proteins implicated in mRNA proce ssing and the translation of a specific subset of mRNAs expressed in differ entiated cells. In lovastatin-treated MDA468 cells, the mobility of the ass ociated hnRNP C1 and C2 proteins changed, and this correlated with increase d p27 expression. Together, these data suggest that the U-rich dependent RN P complex on the 5'UTR may regulate the translation of p27 mRNA and may be a target of antimitogenic signals.