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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 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 hematopoietic cells, was studied in noninduced and LPS-activated macrophages. Analysis of interactions affected by LPS revealed several mRNAs encoding TLR4 downstream kinases and their modulators. We focused on transforming growth factor-?-activated kinase 1 (TAK1) a central player in TLR4 signaling. 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 or stability but enhances TAK1 mRNA translation, resulting in elevated TNF-?, IL-1?, and IL-10 mRNA expression. Our data suggest that the hnRNP K-3' UTR complex inhibits TAK1 mRNA translation in noninduced macrophages. LPS-dependent TLR4 activation abrogates translational repression and newly synthesized TAK1 boosts macrophage inflammatory response.

SUBMITTER: Liepelt A

PROVIDER: S-EPMC4024643 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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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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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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