Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Translation control of TAK1 mRNA by hnRNP K modulates LPS-induced macrophage activation

ABSTRACT: Macrophage activation by bacterial lipopolysaccharides (LPS) is induced through Toll-like receptor 4 (TLR4). The synthesis and activity of TLR4 downstream signalling molecules modulates the expression of pro- and anti-inflammatory cytokines. To address the impact of post-transcriptional regulation on that process, we performed RIP-Chip analysis. Differential association of mRNAs with heterogeneous ribonucleoprotein K (hnRNP K), an mRNA-specific translational regulator in differentiating haematopoietic cells, was studied in non-induced and LPS-activated macrophages. Analysis of interactions affected by LPS revealed an enrichment of mRNAs encoding TLR4 downstream kinases and their modulators. We focused on transforming growth factor Î² activated kinase-1 (TAK1), a central player in TLR4 signalling. HnRNP K interacts specifically with a sequence in the TAK1 mRNA 3' UTR in vitro. Silencing of hnRNP K does not affect TAK1 mRNA synthesis and stability, but enhances TAK1 mRNA translation, resulting in elevated TNF-alpha, IL-1beta and IL-10 mRNA expression. Our data suggest that the hnRNP K-3' UTR complex inhibits TAK1 mRNA translation in non-induced macrophages. LPS-dependent TLR4 activation abrogates translational repression and newly synthesised TAK1 initiates the inflammatory response of macrophages. In this dataset, we include expression data of RAW 264.7 cells comparing untreated cells and 6h Lipopolysaccharide treatment, and analyse RNAs co-precipitating with hnRNP K dependent on LPS treatment. 12 total samples were analyzed, 6 samples of 2 biological replicates.

ORGANISM(S): Mus musculus

SUBMITTER: Bernd Denecke

PROVIDER: E-GEOD-48463 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Translation control of TAK1 mRNA by hnRNP K modulates LPS-induced macrophage activation.

Liepelt Anke A Mossanen Jana C JC Denecke Bernd B Heymann Felix F De Santis Rebecca R Tacke Frank F Marx Gernot G Ostareck Dirk H DH Ostareck-Lederer Antje A

RNA (New York, N.Y.) 20140421 6

Macrophage activation by bacterial lipopolysaccharides (LPS) is induced through Toll-like receptor 4 (TLR4). The synthesis and activity of TLR4 downstream signaling molecules modulates the expression of pro- and anti-inflammatory cytokines. To address the impact of post-transcriptional regulation on that process, we performed RIP-Chip analysis. Differential association of mRNAs with heterogeneous nuclear ribonucleoprotein K (hnRNP K), an mRNA-specific translational regulator in differentiating h ...[more]

PMID: 24751651

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Dataset Information

Translation control of TAK1 mRNA by hnRNP K modulates LPS-induced macrophage activation

Publications

Translation control of TAK1 mRNA by hnRNP K modulates LPS-induced macrophage activation.

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