Document Type
Article
Publication Date
12-1-2017
Abstract
Granulocyte-macrophage colony-stimulating factor (GM-CSF) produced by T helper 17 (Th17) cells plays an essential role in autoimmune diseases. Transcriptional regulation of Th17 cell differentiation has been extensively studied, but post-transcriptional regulation of Th17 cell differentiation has remained less well characterized. The RNA-binding protein HuR functions to promote the stability of target mRNAs via binding the AU-rich elements of the 3' untranslated region (3'UTR) of numerous pro-inflammatory cytokines including IL-4, IL-13, IL-17 and TNF-α. However, whether HuR regulates GM-CSF expression in Th17 cells has not been fully investigated. Here we showed that HuR conditional knockout (KO) Th17 cells have decreased GM-CSF mRNA in comparison with wild-type (WT) Th17 cells, and that HuR binds directly to GM-CSF mRNA 3'UTR. Interestingly, HuR deficiency increased the levels of certain microRNA expression in Th17 cells; for example, miR-466i functioned to mediate GM-CSF and IL-17 mRNA decay, which was confirmed by in vitro luciferase assay. Furthermore, we found that HuR promoted Mxi1 expression to inhibit certain miRNA expression. Taken together, these findings indicate that interaction of HuR and miR-466i orchestrates GM-CSF expression in Th17 cells.
Recommended Citation
Chen, Jing; Adamiak, William; Huang, Ganlei; Atasoy, Ulus; Rostami, Abdolmohamad M.; and Yu, Shiguang, "Interaction of RNA-binding protein HuR and miR-466i regulates GM-CSF expression." (2017). Department of Neurology Faculty Papers. Paper 141.
https://jdc.jefferson.edu/neurologyfp/141
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
PubMed ID
29222492
Comments
This article has been peer reviewed. It is the author’s final published version in Scientific Reports
Volume 7, Issue 1, December 2017, Article number 17233.
The published version is available at DOI: 10.1038/s41598-017-17371-5. Copyright © Chen et al.