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IRAK2 directs stimulus-dependent nuclear export of inflammatory mRNAs
Journal article   Open access

IRAK2 directs stimulus-dependent nuclear export of inflammatory mRNAs

Hao Zhou, Frauke Melchior, Xiaoxia Li, Katarzyna Bulek, Xiao Li, Tomasz Herjan, Minjia Yu, Wen Qian, Han Wang, Gao Zhou, …
eLife, Vol.6, e29630
10/09/2017
DOI: 10.7554/eLife.29630
PMCID: PMC5675595
PMID: 28990926
url
https://doi.org/10.7554/eLife.29630View
Published (Version of record) Open Access

Abstract

Expression of inflammatory genes is determined in part by post-transcriptional regulation of mRNA metabolism but how stimulus- and transcript-dependent nuclear export influence is poorly understood. Here, we report a novel pathway in which LPS/TLR4 engagement promotes nuclear localization of IRAK2 to facilitate nuclear export of a specific subset of inflammation-related mRNAs for translation in murine macrophages. IRAK2 kinase activity is required for LPS-induced RanBP2-mediated IRAK2 sumoylation and subsequent nuclear translocation. Array analysis showed that an SRSF1-binding motif is enriched in mRNAs dependent on IRAK2 for nuclear export. Nuclear IRAK2 phosphorylates SRSF1 to reduce its binding to target mRNAs, which promotes the RNA binding of the nuclear export adaptor ALYREF and nuclear export receptor Nxf1 loading for the export of the mRNAs. In summary, LPS activates a nuclear function of IRAK2 that facilitates the assembly of nuclear export machinery to export selected inflammatory mRNAs to the cytoplasm for translation.
 Cell Biology Immunology Inflammation like receptor Mouse nuclear translocation Research Article RNA export sumoylation toll

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