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Molecular and Cellular Biology, June 2008, p. 4093-4103, Vol. 28, No. 12
0270-7306/08/$08.00+0     doi:10.1128/MCB.00155-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Ribonomic Analysis of Human Pum1 Reveals cis-trans Conservation across Species despite Evolution of Diverse mRNA Target Sets{triangledown} ,{dagger}

Adam R. Morris, Neelanjan Mukherjee, and Jack D. Keene*

Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710

Received 29 January 2008/ Returned for modification 20 March 2008/ Accepted 1 April 2008

PUF family proteins are among the best-characterized regulatory RNA-binding proteins in nonmammalian species, but relatively little is known about mRNA targets or functions of mammalian PUF proteins. In this study, we used ribonomic analysis to identify and analyze mRNAs associated with ribonucleoproteins containing an endogenous human PUF protein, Pum1. Pum1-associated mRNAs were highly enriched for genes encoding proteins that function in transcriptional regulation and cell cycle/proliferation, results consistent with the posttranscriptional RNA regulon model and the proposed ancestral functions of PUF proteins in stem cell biology. Analysis of 3' untranslated region sequences of Pum1-associated mRNAs revealed a core Pum1 consensus sequence, UGUAHAUA. Pum1 knockdown demonstrated that Pum1 enhances decay of associated mRNAs, and relocalization of Pum1 to stress granules suggested that Pum1 functions in repression of translation. This study is the first in vivo genome-wide mRNA target identification of a mammalian PUF protein and provides direct evidence that human PUF proteins regulate stability of associated mRNAs. Comparison of Pum1-associated mRNAs to mRNA targets of PUF proteins from Saccharomyces cerevisiae and Drosophila melanogaster demonstrates how a well-conserved RNA-binding domain and cognate binding sequence have been evolutionarily rewired to regulate the collective expression of different sets of functionally related genes.

* Corresponding author. Mailing address: Box 3020, Research Drive, Duke University Medical Center, Durham, NC 27710. Phone: (919) 684-5138. Fax: (919) 684-8735. E-mail: keene001{at}mc.duke.edu

{triangledown} Published ahead of print on 14 April 2008.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, June 2008, p. 4093-4103, Vol. 28, No. 12
0270-7306/08/$08.00+0     doi:10.1128/MCB.00155-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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