| First Author | Huang W | Year | 2015 |
| Journal | Nature | Volume | 528 |
| Issue | 7583 | Pages | 517-22 |
| PubMed ID | 26675721 | Mgi Jnum | J:228279 |
| Mgi Id | MGI:5706647 | Doi | 10.1038/nature16193 |
| Citation | Huang W, et al. (2015) DDX5 and its associated lncRNA Rmrp modulate TH17 cell effector functions. Nature 528(7583):517-22 |
| abstractText | T helper 17 (TH17) lymphocytes protect mucosal barriers from infections, but also contribute to multiple chronic inflammatory diseases. Their differentiation is controlled by RORgammat, a ligand-regulated nuclear receptor. Here we identify the RNA helicase DEAD-box protein 5 (DDX5) as a RORgammat partner that coordinates transcription of selective TH17 genes, and is required for TH17-mediated inflammatory pathologies. Surprisingly, the ability of DDX5 to interact with RORgammat 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-RORgammat interaction and RORgammat target gene transcription. Elucidation of the link between Rmrp and the DDX5-RORgammat 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. |
