Gene expression is precisely regulated during the inflammatory response to control infection and limit the detrimental effects of inflammation. Here, we profiled global mRNA translation dynamics in the mouse primary macrophage-mediated inflammatory response and identified hundreds of differentially translated mRNAs. These mRNAs' 3'UTRs have enriched binding motifs for several RNA-binding proteins, which implies extensive translational regulatory networks. We characterized one such protein, Zfp36, as a translation repressor. Using primary macrophages from a Zfp36-V5 epitope tagged knock-in mouse generated by CRISPR/Cas9-mediated genome editing, we found that the endogenous Zfp36 directly interacts with the cytoplasmic poly(A)-binding protein. Importantly, this interaction is required for the translational repression of Zfp36's target mRNAs in resolving inflammation. Altogether, these results uncovered critical roles of translational regulations in controlling appropriate gene expression during the inflammatory response and revealed a new biologically relevant molecular mechanism of translational repression via modulating the cytoplasmic poly(A)-binding protein.
Gene Expression OmnibusPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE99787).
- Wenqian Hu
- Wenqian Hu
- Shaojie Zhang
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: All the procedures on the isolation of BMDMs from mice were performed under a protocol (A35015) approved by the Mayo Clinic animal welfare committee.
- Torben Heick Jensen, Aarhus University, Denmark
© 2017, Zhang et al.
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