HuR promotes miRNA-mediated upregulation of NFI-A protein expression in MDSCs during murine sepsis.
MDSC
NFI-A
Sepsis
miRNA
Journal
Molecular immunology
ISSN: 1872-9142
Titre abrégé: Mol Immunol
Pays: England
ID NLM: 7905289
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
23
12
2019
revised:
09
04
2020
accepted:
14
04
2020
pubmed:
1
6
2020
medline:
19
8
2020
entrez:
1
6
2020
Statut:
ppublish
Résumé
Myeloid-derived suppressor cells (MDSCs) contribute to high mortality rates during sepsis, but how sepsis induces MDSCs is unclear. Previously we reported that microRNA (miR)-21 and miR-181b reprogram MDSCs in septic mice by increasing levels of DNA binding transcription factor, nuclear factor 1 (NFI-A). Here, we provide evidence that miR-21 and miR-181b stabilize NFI-A mRNA and increase NFI-A protein levels by recruiting RNA-binding proteins HuR and Ago1 to its 3' untranslated region (3'UTR). We also find that the NFI-A GU-rich element (GRE)-binding protein CUGBP1 counters miR-21 and miR-181b dependent NFI-A mRNA stabilization and decreases protein production by replacing 3'UTR bound Ago1 with Ago2. We confirmed the miR-21 and miR-181b dependent reprogramming pathway in MDSCs transfected with a luciferase reporter construct containing an NFI-A 3'UTR fragment with point mutations in the miRNA binding sites. These results suggest that targeting NFI-A in MDSCs during sepsis may enhance resistance to uncontrolled infection.
Identifiants
pubmed: 32474254
pii: S0161-5890(19)30920-4
doi: 10.1016/j.molimm.2020.04.014
pmc: PMC7519576
mid: NIHMS1599038
pii:
doi:
Substances chimiques
ELAV-Like Protein 1
0
Elavl1 protein, mouse
0
MIRN-21 microRNA, mouse
0
MicroRNAs
0
NFI Transcription Factors
0
Nfia protein, mouse
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
97-105Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM103887
Pays : United States
Commentaires et corrections
Type : ErratumIn
Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest None.
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