PUBLICATION
Post-transcriptional regulation of Nrf2-mRNA by the mRNA-binding proteins HuR and AUF1
- Authors
- Poganik, J.R., Long, M.J.C., Disare, M.T., Liu, X., Chang, S.H., Hla, T., Aye, Y.
- ID
- ZDB-PUB-191102-1
- Date
- 2019
- Source
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology 33(12): 14636-14652 (Journal)
- Registered Authors
- Aye, Yimon, Poganik, Jesse
- Keywords
- antioxidant response, mRNA-maturation, mRNA-stabilization, mRNA-trafficking, zebrafish
- MeSH Terms
-
- Animals
- Cells, Cultured
- ELAV-Like Protein 1/genetics
- ELAV-Like Protein 1/metabolism*
- HEK293 Cells
- Heterogeneous Nuclear Ribonucleoprotein D0/metabolism*
- Humans
- Mice
- NF-E2-Related Factor 2/metabolism*
- Protein Binding
- RNA Processing, Post-Transcriptional*
- RNA Transport
- RNA, Messenger/genetics
- RNA, Messenger/metabolism
- Zebrafish
- PubMed
- 31665914 Full text @ FASEB J.
Citation
Poganik, J.R., Long, M.J.C., Disare, M.T., Liu, X., Chang, S.H., Hla, T., Aye, Y. (2019) Post-transcriptional regulation of Nrf2-mRNA by the mRNA-binding proteins HuR and AUF1. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 33(12):14636-14652.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping