Translation control of TAK1 mRNA by hnRNP K modulates LPS-induced macrophage activation.
RNA
; 20(6): 899-911, 2014 Jun.
Article
in En
| MEDLINE
| ID: mdl-24751651
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-ß-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-α, IL-1ß, 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Protein Biosynthesis
/
RNA, Messenger
/
Lipopolysaccharides
/
MAP Kinase Kinase Kinases
/
Heterogeneous-Nuclear Ribonucleoprotein K
/
Macrophage Activation
/
Macrophages
Limits:
Animals
Language:
En
Journal:
RNA
Journal subject:
BIOLOGIA MOLECULAR
Year:
2014
Type:
Article
Affiliation country:
Germany