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Nucleic Acids Research, 2001, Vol. 29, No. 5 1156-1162
© 2001 Oxford University Press

Polysomal ribonuclease 1 exists in a latent form on polysomes prior to estrogen activation of mRNA decay

Kristopher S. Cunningham1, Mark N. Hanson2 and Daniel R. Schoenberg*

Department of Molecular and Cellular Biochemistry and Comprehensive Cancer Center, 1Ohio State Biochemistry Program and 2Molecular, Cellular and Developmental Biology Program, The Ohio State University, Columbus, OH 43210, USA

Estrogen induces a global change in the translation profile of Xenopus hepatocytes, replacing serum protein synthesis with production of the yolk protein precursor vitellogenin. This is accomplished by the coordinate destabilization of serum protein mRNAs and the transcriptional induction and subsequent stabilization of vitellogenin mRNA. Previous work identified an endonuclease activity whose appearance on polysomes correlated with the disappearance of serum protein mRNAs. This enzyme, polysomal ribonuclease 1 (PMR1), is a novel member of the peroxidase gene family. The current study examined the association of PMR1 with its mRNA targets on polysomes and mRNPs. The highest amount of polysome-bound PMR1 was observed prior to estrogen induction of mRNA decay. Its distribution on sucrose density gradients matched the absorbance profile of polysome-bound mRNA, suggesting that PMR1 forms a latent complex with mRNA. Following dissociation with EDTA the 62 kDa PMR1 sedimented with a larger complex of >670 kDa. Estrogen induces a 22-fold increase in unit enzymatic activity of polysome-bound PMR1, and a time-dependent loss of PMR1 from polysomes in a manner that mirrors the disappearance of albumin mRNA. These data suggest that the key step in the extensive estrogen-induced change in mRNA decay in Xenopus liver is activation of a latent mRNA endonuclease associated with its target mRNA.

* To whom correspondence should be addressed at: Department of Molecular and Cellular Biochemistry, The Ohio State University, 1645 Neil Avenue, Columbus, OH 43210-1218, USA. Tel: +1 614 688 3012; Fax: +1 614 292 7232; Email: schoenberg.3{at}osu.edu Present address: Kristopher S. Cunningham, University of Ottawa School of Medicine, Ottawa, Ontario, Canada


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