Noncoding RNA MaIL1 is an integral component of the TLR4-TRIF pathway.

Autor:	Aznaourova M; Institute for Lung Research, Philipps-University, 35043 Marburg, Germany., Janga H; Institute for Lung Research, Philipps-University, 35043 Marburg, Germany., Sefried S; Institute for Lung Research, Philipps-University, 35043 Marburg, Germany., Kaufmann A; Institute for Immunology, Philipps-University, 35043 Marburg, Germany., Dorna J; Institute for Immunology, Philipps-University, 35043 Marburg, Germany., Volkers SM; Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 13353 Berlin, Germany., Georg P; Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 13353 Berlin, Germany., Lechner M; Center for Synthetic Microbiology, Philipps-University, 35043 Marburg, Germany.; Institute for Pharmaceutical Chemistry, Philipps-University, 35037 Marburg, Germany., Hoppe J; Department of Veterinary Pathology, Freie Universität Berlin, 14163 Berlin, Germany., Dökel S; Department of Veterinary Pathology, Freie Universität Berlin, 14163 Berlin, Germany., Schmerer N; Institute for Lung Research, Philipps-University, 35043 Marburg, Germany., Gruber AD; Department of Veterinary Pathology, Freie Universität Berlin, 14163 Berlin, Germany., Linne U; Department of Chemistry, Philipps-University, 35043 Marburg, Germany., Bauer S; Institute for Immunology, Philipps-University, 35043 Marburg, Germany., Sander LE; Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 13353 Berlin, Germany.; German Center for Lung Research, 35392 Giessen, Germany., Schmeck B; Institute for Lung Research, Philipps-University, 35043 Marburg, Germany.; Center for Synthetic Microbiology, Philipps-University, 35043 Marburg, Germany.; German Center for Lung Research, 35392 Giessen, Germany.; Department of Respiratory and Critical Care Medicine, University Medical Center Marburg, 35043 Marburg, Germany.; Universities of Giessen and Marburg Lung Centre, 35043 Marburg, Germany., Schulte LN; Institute for Lung Research, Philipps-University, 35043 Marburg, Germany; leon.schulte@uni-marburg.de.; German Center for Lung Research, 35392 Giessen, Germany.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2020 Apr 21; Vol. 117 (16), pp. 9042-9053. Date of Electronic Publication: 2020 Apr 02.
DOI:	10.1073/pnas.1920393117
Abstrakt:	RNA has been proposed as an important scaffolding factor in the nucleus, aiding protein complex assembly in the dense intracellular milieu. Architectural contributions of RNA to cytosolic signaling pathways, however, remain largely unknown. Here, we devised a multidimensional gradient approach, which systematically locates RNA components within cellular protein networks. Among a subset of noncoding RNAs (ncRNAs) cosedimenting with the ubiquitin-proteasome system, our approach unveiled ncRNA MaIL1 as a critical structural component of the Toll-like receptor 4 (TLR4) immune signal transduction pathway. RNA affinity antisense purification-mass spectrometry (RAP-MS) revealed MaIL1 binding to optineurin (OPTN), a ubiquitin-adapter platforming TBK1 kinase. MaIL1 binding stabilized OPTN, and consequently, loss of MaIL1 blunted OPTN aggregation, TBK1-dependent IRF3 phosphorylation, and type I interferon (IFN) gene transcription downstream of TLR4. MaIL1 expression was elevated in patients with active pulmonary infection and was highly correlated with IFN levels in bronchoalveolar lavage fluid. Our study uncovers MaIL1 as an integral RNA component of the TLR4-TRIF pathway and predicts further RNAs to be required for assembly and progression of cytosolic signaling networks in mammalian cells. Competing Interests: The authors declare no competing interest.
Databáze:	MEDLINE
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