Talk on Saturday 12:00-12:20pm submitted by Wenqian Hu
Translation repression via modulating the cytoplasmic poly(A) binding protein in inflammatory response
Xu Zhang (Biochemistry and Molecular Biology, Mayo Clinic), Xiaoli Chen (University of Central Florida), Qiuying Liu (Biochemistry and Molecular Biology, Mayo Clinic), Shaojie Zhang (University of Central Florida), Wenqian Hu (Biochemistry and Molecular Biology, Mayo Clinic)
Gene expression is precisely regulated in inflammatory response to control infection and limit detrimental effects of inflammation. Here, we profiled global mRNA translation dynamics in mouse primary macrophage-mediated inflammatory response and identified hundreds of differentially translated mRNAs. These mRNAs’ 3’UTRs have enriched binding motifs of several RNA-binding proteins, implying extensive translational regulatory networks. We characterized one such protein, Zfp36, as a translation repressor. Using primary macrophages from a Zfp36-V5 epitope tag 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 inflammatory responses and revealed a new biologically relevant molecular mechanism of translational repression via modulating the cytoplasmic poly(A) binding protein.
Keywords: translational control , poly(A) binding protein, Zfp36