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PMID: 18367721 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Identification of TTP mRNA targets in human dendritic cells reveals TTP as a critical regulator of dendritic cell maturation.

RNA (New York, N.Y.) ·Vol. 14 ·No. 5 ·2008-05-00 ·Pages 888-902

Emmons J, Townley-Tilson WH, Deleault KM, Skinner SJ, Gross RH, Whitfield ML, Brooks SA

Abstract

Dendritic cells provide a critical link between innate and adaptive immunity and are essential to prime a naive T-cell response. The transition from immature dendritic cells to mature dendritic cells involves numerous changes in gene expression; however, the role of post-transcriptional changes in this process has been largely ignored. Tristetraprolin is an AU-rich element mRNA-binding protein that has been shown to regulate the stability of a number of cytokines and chemokines of mRNAs. Using TTP immunoprecipitations and Affymetrix GeneChips, we identified 393 messages as putative TTP mRNA targets in human dendritic cells. Gene ontology analysis revealed that approximately 25% of the identified mRNAs are associated with protein synthesis. We also identified six MHC Class I alleles, five MHC Class II alleles, seven chemokine and chemokine receptor genes, indoleamine 2,3 dioxygenase, and CD86 as putative TTP ligands. Real-time PCR was used to validate the GeneChip data for 15 putative target genes and functional studies performed for six target genes. These data establish that TTP regulates the expression of DUSP1, IDO, SOD2, CD86, and MHC Class I-B and F via the 3'-untranslated region of each gene. A novel finding is the demonstration that TTP can interact with and regulate the expression of non-AU-rich element-containing messages. The data implicate TTP as having a broader role in regulating and limiting the immune response than previously suspected.

MeSH Terms
3' Untranslated Regions B7-2 Antigen/genetics Base Sequence Cell Differentiation/genetics,immunology,physiology Chemokines/genetics DNA/genetics Dendritic Cells/cytology,immunology,metabolism Gene Expression Regulation Genes, MHC Class I Genes, MHC Class II Genes, Reporter Humans Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics Ligands Molecular Sequence Data Oligonucleotide Array Sequence Analysis Polymerase Chain Reaction RNA, Messenger/genetics,metabolism Receptors, Chemokine/genetics Sequence Homology, Nucleic Acid Tristetraprolin/genetics,immunology,metabolism
Chemicals
3' Untranslated Regions B7-2 Antigen CD86 protein, human Chemokines Indoleamine-Pyrrole 2,3,-Dioxygenase Ligands RNA, Messenger Receptors, Chemokine Tristetraprolin ZFP36 protein, human DNA
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Emmons Jillian
Department of Microbiology and Immunology, Dartmouth Medical School, Hanover, New Hampshire 03755, USA.
Townley-Tilson W H Davin
Deleault Kristen M
Skinner Stephen J
Gross Robert H
Whitfield Michael L
Brooks Seth A
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Article Info
Journal
RNA (New York, N.Y.)
Abbr.
RNA
ISSN
1469-9001
DOI
10.1261/rna.748408
Published
2008-05-00
Epub
2008-00-26
Pages
888-902
Language
English
Region
United States
NLM ID
9509184
PMCID
PMC2327351
Subset
IM
Grants
Howard Hughes Medical Institute · 76200-560801 · United States
External Links
PubMed source DOI: 10.1261/rna.748408 PMC Full Text View journal details
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