@article{9b2158e7df9743dfae02817b30d29918,
title = "DDX5 and its associated lncRNA Rmrp modulate TH17 cell effector functions",
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.",
author = "Wendy Huang and Benjamin Thomas and Flynn, {Ryan A.} and Gavzy, {Samuel J.} and Lin Wu and Kim, {Sangwon V.} and Hall, {Jason A.} and Miraldi, {Emily R.} and Ng, {Charles P.} and Rigo, {Frank W.} and Sarah Meadows and Montoya, {Nina R.} and Herrera, {Natalia G.} and Domingos, {Ana I.} and Fraydoon Rastinejad and Myers, {Richard M.} and Fuller-Pace, {Frances V.} and Richard Bonneau and Chang, {Howard Y.} and Oreste Acuto and Littman, {Dan R.}",
note = "Funding Information: Acknowledgements We thank M. V. Pokrovskii for unpublished ATAC-seq data and L. X. Garmire for suggestions on our manuscript. This work was supported by a Cancer Research Institute Irvington Postdoctoral Fellowship (W.H.), Institutional NRSA T32 CA009161_Levy (W.H.), National Multiple Sclerosis Society postdoctoral fellowship FG 2089-A-1 (L.W.), Career Development Award (329388) from the Crohn{\textquoteright}s and Colitis Foundation of America (S.V.K.), Dale and Betty Frey Fellowship of the Damon Runyon Cancer Research Foundation 2105-12 (J.A.H.), HHMI Exceptional Research Opportunities Program (N.R.M. and N.H.), NIH F30 1F30CA189514-01 (R.A.F.), NIH P50-HG007735 and R01HG004361 (H.Y.C.), NIH R01AI080885 (D.R.L.), NIH R01DK103358 (R.B. and D.R.L.), and the Howard Hughes Medical Institute (H.Y.C. and D.R.L.). Publisher Copyright: {\textcopyright} 2015 Macmillan Publishers Limited. All rights reserved.",
year = "2015",
month = dec,
day = "24",
doi = "10.1038/nature16193",
language = "English (US)",
volume = "528",
pages = "517--522",
journal = "Nature Cell Biology",
issn = "1465-7392",
publisher = "Nature Publishing Group",
number = "7583",
}