Premium
Post‐transcriptional regulation of Nrf2‐mRNA by the mRNA‐binding proteins HuR and AUF1
Author(s) -
Poganik Jesse R.,
Long Marcus J. C.,
Disare Michael T.,
Liu Xuyu,
Chang SungHee,
Hla Timothy,
Aye Yimon
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201901930r
Subject(s) - messenger rna , untranslated region , three prime untranslated region , rna binding protein , transcriptional regulation , microbiology and biotechnology , biology , chemistry , gene , gene expression , genetics
The nuclear factor erythroid 2‐related factor 2 (Nrf2) signaling axis is a target of covalent drugs and bioactive native electrophiles. However, much of our understanding of Nrf2 regulation has been focused at the protein level. 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 RNA‐sequencing data and subsequent mechanistic analyses led us to discover a novel role of HuR in regulating Nrf2 activity, and in the process, we further identified the related mRBP AUF1 as an additional novel Nrf2 regulator. Both mRBPs regulate Nrf2 activity 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 a Nrf2 activity‐reporter zebrafish strain, we document that this post‐transcriptional control of Nrf2 activity is conserved at the whole‐vertebrate level.—Poganik, J. R., Long, M. J. C., Disare, M. T., Liu, X., Chang, S.‐H., Hla, T., Aye, Y. Post‐transcriptional regulation of Nrf2‐mRNA by the mRNA‐binding proteins HuR and AUF1. FASEB J. 33, 14636‐14652 (2019). www.fasebj.org