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DDX5 and its associated lncRNA Rmrp modulate TH17 cell effector functions

Open access
Huang, Wendy, Thomas, Benjamin, Flynn, Ryan A., Gavzy, Samuel J., Wu, Lin, Kim, Sangwon V., Hall, Jason A., Miraldi, Emily R., Ng, Charles P., Rigo, Frank, Meadows, Sarah, Montoya, Nina R., Herrera, Natalia G., Domingos, Ana I., Rastinejad, Fraydoon, Myers, Richard M., Fuller-Pace, Frances V., Bonneau, Richard, Chang, Howard Y., Acuto, Oreste, Littman, Dan R.·2015·Nature

Abstract

T helper 17 (TH17) lymphocytes protect mucosal barriers from infections, but also contribute to multiple chronic inflammatory diseases. Their differentiation is controlled by RORγt, a ligand-regulated nuclear receptor. Here we identify the RNA helicase DEAD-box protein 5 (DDX5) as a RORγt partner that coordinates transcription of selective TH17 genes, and is required for TH17-mediated inflammatory pathologies. Surprisingly, the ability of DDX5 to interact with RORγt and coactivate its targets depends on intrinsic RNA helicase activity and binding of a conserved nuclear long noncoding RNA (lncRNA), Rmrp, which is mutated in patients with cartilage-hair hypoplasia. A targeted Rmrp gene mutation in mice, corresponding to a gene mutation in cartilage-hair hypoplasia patients, altered lncRNA chromatin occupancy, and reduced the DDX5–RORγt interaction and RORγt target gene transcription. Elucidation of the link between Rmrp and the DDX5–RORγt complex reveals a role for RNA helicases and lncRNAs in tissue-specific transcriptional regulation, and provides new opportunities for therapeutic intervention in TH17-dependent diseases.

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Metadata

Authors
Huang, W., Thomas, B., Flynn, R. A., Gavzy, S. J., Wu, L., Kim, S. V., Hall, J. A., Miraldi, E. R., Ng, C. P., Rigo, F., Meadows, S., Montoya, N. R., Herrera, N. G., Domingos, A. I., Rastinejad, F., Myers, R. M., Fuller-Pace, F. V., Bonneau, R., Chang, H. Y., Acuto, O., & Littman, D. R.
Venue
Nature
Published
2015-12-16
Volume
528
Issue
7583
Pages
517-522
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W2206191771
Cited by
167
References
7
FWCI
13.05
Type
journal article
Language
en
Status
Retracted
Open access
bronze

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CoChat. (2026). Citation check: DDX5 and its associated lncRNA Rmrp modulate TH17 cell effector functions. https://app.cochat.ai/papers/10.1038/nature16193
The paper
Huang, W., Thomas, B., Flynn, R. A., Gavzy, S. J., Wu, L., Kim, S. V., Hall, J. A., Miraldi, E. R., Ng, C. P., Rigo, F., Meadows, S., Montoya, N. R., Herrera, N. G., Domingos, A. I., Rastinejad, F., Myers, R. M., Fuller-Pace, F. V., Bonneau, R., Chang, H. Y., . . . Littman, D. R. (2015). DDX5 and its associated lncRNA Rmrp modulate TH17 cell effector functions. Nature. https://doi.org/10.1038/nature16193

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.