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bioRxiv · 10.1101/565937

Post-transcriptional regulation of Nrf2-mRNA by the mRNA-binding proteins HuR and AUF1

Poganik, J. R.·Long, M. J.·Disare, M. T.·Liu, X.·Chang, S.-H.·Hla, T.·Aye, Y.
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Abstract

The Nrf2-driven antioxidant response (AR) is a target of covalent drugs and bioactive native electrophiles. However, much of our understanding of AR has centered on protein-level regulation of Nrf2. Here we report a post-transcriptional modality to directly regulate Nrf2-mRNA. Our initial studies focused on the effects of the key mRNA-binding protein (mRBP) HuR on global transcriptomic changes incurred upon oxidant or electrophile stimulation. These data led us to discover a novel role of HuR in regulating Nrf2/AR, and in the process we further identified the related mRBP AUF1 as an additional novel Nrf2/AR regulator. Both mRBPs regulate AR by direct interaction with the Nrf2 transcript. Our data showed that HuR enhances Nrf2-mRNA maturation and promotes its nuclear export; whereas AUF1 stabilizes Nrf2-mRNA. Both mRBPs target the 3'-UTR of Nrf2-mRNA. Using an AR-reporter zebrafish strain, we document that this post-transcriptional control of AR is conserved at the whole-vertebrate level.

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Poganik, J. R., Long, M. J., Disare, M. T., Liu, X., Chang, S.-H., Hla, T., Aye, Y.. 2019-03-03. Post-transcriptional regulation of Nrf2-mRNA by the mRNA-binding proteins HuR and AUF1. https://doi.org/10.1101/565937

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