DDX5 and its associated lncRNA Rmrp modulate [T.sub.H]17 cell effector functions

T helper 17 ([T.sub.H]17) 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 [T.sub.H]17 genes, and is required for [T.sub.H]17-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 [T.sub.H]17-dependent diseases.
[T.sub.H]17 cells are [CD4.sup.+] lymphocytes that help to protect mucosal epithelial barriers against bacterial and fungal infections (1), and are also important in multiple autoimmune diseases (2-7). The [T.sub.H]17 cell [...]