DDX5 and its associated lncRNA Rmrp modulate TH17 cell effector functions
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..
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2015 |
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| Erschienen: |
2015 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:528 |
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| Enthalten in: |
Nature |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Huang, Wendy [VerfasserIn] |
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| Links: |
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| doi: |
10.1038/nature16193 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
OLC1969683643 |
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| 100 | 1 | |a Huang, Wendy |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a DDX5 and its associated lncRNA Rmrp modulate TH17 cell effector functions |
| 264 | 1 | |c 2015 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
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| 520 | |a 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. | ||
| 650 | 4 | |a Hair - abnormalities | |
| 650 | 4 | |a Transcription, Genetic - genetics | |
| 650 | 4 | |a Immunologic Deficiency Syndromes - genetics | |
| 650 | 4 | |a Th17 Cells - metabolism | |
| 650 | 4 | |a DEAD-box RNA Helicases - metabolism | |
| 650 | 4 | |a RNA, Long Noncoding - genetics | |
| 650 | 4 | |a Nuclear Receptor Subfamily 1, Group F, Member 3 - metabolism | |
| 650 | 4 | |a Chromatin - metabolism | |
| 650 | 4 | |a Th17 Cells - immunology | |
| 650 | 4 | |a Hirschsprung Disease - genetics | |
| 650 | 4 | |a Osteochondrodysplasias - congenital | |
| 650 | 4 | |a Gene Expression Regulation - genetics | |
| 650 | 4 | |a Inflammation - pathology | |
| 650 | 4 | |a Chromatin - genetics | |
| 650 | 4 | |a Mutation - genetics | |
| 650 | 4 | |a Inflammation - immunology | |
| 650 | 4 | |a DEAD-box RNA Helicases - genetics | |
| 650 | 4 | |a RNA, Long Noncoding - metabolism | |
| 650 | 4 | |a Osteochondrodysplasias - genetics | |
| 700 | 1 | |a Thomas, Benjamin |4 oth | |
| 700 | 1 | |a Flynn, Ryan A |4 oth | |
| 700 | 1 | |a Gavzy, Samuel J |4 oth | |
| 700 | 1 | |a Wu, Lin |4 oth | |
| 700 | 1 | |a Kim, Sangwon V |4 oth | |
| 700 | 1 | |a Hall, Jason A |4 oth | |
| 700 | 1 | |a Miraldi, Emily R |4 oth | |
| 700 | 1 | |a Ng, Charles P |4 oth | |
| 700 | 1 | |a Rigo, Frank W |4 oth | |
| 700 | 1 | |a Meadows, Sarah |4 oth | |
| 700 | 1 | |a Montoya, Nina R |4 oth | |
| 700 | 1 | |a Herrera, Natalia G |4 oth | |
| 700 | 1 | |a Domingos, Ana I |4 oth | |
| 700 | 1 | |a Rastinejad, Fraydoon |4 oth | |
| 700 | 1 | |a Myers, Richard M |4 oth | |
| 700 | 1 | |a Fuller-Pace, Frances V |4 oth | |
| 700 | 1 | |a Bonneau, Richard |4 oth | |
| 700 | 1 | |a Chang, Howard Y |4 oth | |
| 700 | 1 | |a Acuto, Oreste |4 oth | |
| 700 | 1 | |a Littman, Dan R |4 oth | |
| 773 | 0 | 8 | |i Enthalten in |t Nature <London> |d London : Macmillan, 1869 |g 528(2015), 7583, Seite 517-522 |w (DE-627)129292834 |w (DE-600)120714-3 |w (DE-576)014473941 |x 0028-0836 |7 nnns |
| 773 | 1 | 8 | |g volume:528 |g year:2015 |g number:7583 |g pages:517-522 |
| 856 | 4 | 1 | |u http://dx.doi.org/10.1038/nature16193 |3 Volltext |
| 856 | 4 | 2 | |u http://www.ncbi.nlm.nih.gov/pubmed/26675721 |
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