DDX5 and its associated lncRNA Rmrp modulate TH17 cell effector functions
Wendy Huang1, Benjamin Thomas2, Ryan A Flynn3
1The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, New York 10016, USA.
Nature
|December 18, 2015
Summary
DEAD-box protein 5 (DDX5), an RNA helicase, partners with RORγt to regulate T helper 17 (TH17) cell differentiation. This interaction, dependent on the Rmrp long noncoding RNA, is crucial for TH17-mediated inflammation.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- T helper 17 (TH17) cells are vital for mucosal immunity but implicated in chronic inflammatory diseases.
- TH17 cell differentiation is regulated by the nuclear receptor RORγt.
Purpose of the Study:
- To identify novel partners of RORγt involved in TH17 cell function.
- To elucidate the role of RNA helicases and long noncoding RNAs in TH17-mediated pathologies.
Main Methods:
- Co-immunoprecipitation to identify protein interactions.
- RNA-binding assays to assess lncRNA involvement.
- Gene expression analysis to quantify target gene transcription.
- Mouse models with targeted gene mutations.
Main Results:
- DEAD-box protein 5 (DDX5) identified as a RORγt-interacting partner.
- DDX5's interaction with RORγt and transcriptional coactivation depend on its RNA helicase activity and the Rmrp lncRNA.
- A mouse model mimicking cartilage-hair hypoplasia mutation in Rmrp showed impaired DDX5-RORγt interaction and reduced TH17 gene transcription.
Conclusions:
- DDX5 and Rmrp are essential components of the RORγt transcriptional complex regulating TH17 cell differentiation.
- The findings reveal a novel mechanism involving RNA helicases and lncRNAs in tissue-specific gene regulation.
- This study offers potential therapeutic targets for TH17-dependent inflammatory diseases.
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