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PMID: 18256032 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Genome-wide analysis identifies interleukin-10 mRNA as target of tristetraprolin.

The Journal of biological chemistry ·Vol. 283 ·No. 17 ·2008-04-25 ·Pages 11689-99

Stoecklin G, Tenenbaum SA, Mayo T, Chittur SV, George AD, Baroni TE, Blackshear PJ, Anderson P

Abstract

Tristetraprolin (TTP) is an RNA-binding protein required for the rapid degradation of mRNAs containing AU-rich elements. Targets regulated by TTP include the mRNAs encoding tumor necrosis factor-alpha, granulocyte-macrophage colony-stimulating factor, interleukin-2 (IL-2), and immediate early response 3. To identify novel target mRNAs of TTP in macrophages, we used a genome-wide approach that combines RNA immunoprecipitation and microarray analysis. A list was compiled of 137 mRNAs that are associated with TTP with an estimated accuracy on the order of 90%. Sequence analysis revealed a highly significant enrichment of AU-rich element motifs, with AUUUA pentamers present in 96% and UUAUUUAUU nonamers present in 44% of TTP-associated mRNAs. We further show that IL-10 is a novel target regulated by TTP. IL-10 mRNA levels were found to be elevated because of a reduced decay rate in primary macrophages from TTP(-/-) mice. Our study demonstrates the importance of experimental approaches for identifying targets of RNA-binding proteins.

MeSH Terms
3' Untranslated Regions Animals Cell Line Gene Expression Regulation Genome Inflammation Interleukin-10/metabolism Macrophages/metabolism Mice Models, Biological Oligonucleotide Array Sequence Analysis Protein Structure, Tertiary RNA Stability RNA, Messenger/metabolism Tristetraprolin/metabolism
Chemicals
3' Untranslated Regions RNA, Messenger Tristetraprolin Interleukin-10
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Stoecklin Georg
Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. [email protected]
Tenenbaum Scott A
Mayo Thomas
Chittur Sridar V
George Ajish D
Baroni Timothy E
Blackshear Perry J
Anderson Paul
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Article Info
Journal
The Journal of biological chemistry
Abbr.
J Biol Chem
ISSN
0021-9258
DOI
10.1074/jbc.M709657200
Email
[email protected]
Published
2008-04-25
Epub
2008-00-06
Pages
11689-99
Language
English
Region
United States
NLM ID
2985121R
PMCID
PMC2431067
Subset
IM
Grants
NIAID NIH HHS · AI-33600 · United States
NIAID NIH HHS · AI-50167 · United States
NHGRI NIH HHS · R21HG003679 · United States
NHGRI NIH HHS · U01HG004571 · United States
External Links
PubMed source DOI: 10.1074/jbc.M709657200 PMC Full Text View journal details
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