Publikationsdatenbank

Noncoding RNA MaIL1 is an integral component of the TLR4-TRIF pathway (2020)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Aznaourova, Marina

Janga, Harshavardhan

Sefried, Stephanie

Kaufmann, Andreas

Dorna, Jens

Volkers, Sarah M.

Georg, Philipp

Lechner, Marcus

Hoppe, Judith (WE 12)

Dökel, Simon (WE 12)

Schmerer, Nils

Gruber, Achim D. (WE 12)

Linne, Uwe

Bauer, Stefan

Sander, Leif E.

Schmeck, Bernd

Schulte, Leon N.

Quelle

Proceedings of the National Academy of Sciences of the United States of America

Bandzählung: 117

Heftzählung: 16

Seiten: 9042 – 9053

ISSN: 1091-6490

Sprache

Englisch

Verweise

URL (Volltext): https://www.pnas.org/content/117/16/9042

DOI: 10.1073/pnas.1920393117

Pubmed: 32241891

Kontakt

Institut für Tierpathologie

Robert-von-Ostertag-Str. 15
14163 Berlin
+49 30 838 62450
pathologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

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.