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Molecular and Cellular Biology, January 2009, p. 458-470, Vol. 29, No. 2
0270-7306/09/$08.00+0 doi:10.1128/MCB.00824-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Genome-Wide Polysome Profiling Reveals an Inflammation-Responsive Posttranscriptional Operon in Gamma Interferon-Activated Monocytes
,
Keyur Vyas,1,
Sujan Chaudhuri,1,
Douglas W. Leaman,2
Anton A. Komar,1
Alla Musiyenko,3
Sailen Barik,3 and
Barsanjit Mazumder1*
Center for Gene Regulation in Health and Disease and Department of Biology, Geology and Environmental Sciences, Cleveland State University, Cleveland, Ohio 44115,1 Department of Biological Sciences, University of Toledo, Toledo, Ohio 43606,2 Department of Biochemistry and Molecular Biology, University of South Alabama, College of Medicine, Mobile, Alabama 366883
Received 21 May 2008/ Returned for modification 26 June 2008/ Accepted 1 November 2008
We previously showed that ribosomal protein L13a is required for translational silencing of gamma interferon (IFN-
)-induced ceruloplasmin (Cp) synthesis in monocytes. This silencing also requires the presence of the GAIT (IFN-gamma activated inhibitor of translation) element in the 3' untranslated region (UTR) of Cp mRNA. Considering that Cp is an inflammatory protein, we hypothesized that this mechanism may have evolved to silence a family of proinflammatory proteins, of which Cp is just one member. To identify the other mRNAs that are targets for this silencing, we performed a genome-wide analysis of the polysome-profiled mRNAs by using an Affymetrix GeneChip and an inflammation-responsive gene array. A cluster of mRNAs encoding different chemokines and their receptors was identified as common hits in the two approaches and validated by real-time PCR. In silico predicted GAIT hairpins in the 3' UTRs of the target mRNAs were confirmed as functional cis-acting elements for translational silencing by luciferase reporter assays. Consistent with Cp, the newly identified target mRNAs also required L13a for silencing. Our studies have identified a new inflammation-responsive posttranscriptional operon that can be regulated directly at the level of translation in IFN--activated monocytes. This regulation of a cohort of mRNAs encoding inflammatory proteins may be important to resolve inflammation.
* Corresponding author. Mailing address: Center for Gene Regulation in Health and Disease and Departments of Biology, Geology, and Environmental Sciences, Cleveland State University, SR 261, 2121 Euclid Avenue, Cleveland, OH 44115. Phone: (216) 687-2435. Fax: (216) 687-6972. E-mail: b.mazumder{at}csuohio.edu
Published ahead of print on 10 November 2008.
Supplemental material for this article may be found at http://mcb.asm.org/.
K.V. and S.C. contributed equally to this work.
Molecular and Cellular Biology, January 2009, p. 458-470, Vol. 29, No. 2
0270-7306/09/$08.00+0 doi:10.1128/MCB.00824-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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