Abstract
Roquin is an RNA-binding protein that prevents autoimmunity and inflammation via repression of bound target mRNAs such as inducible costimulator (Icos). When Roquin is absent or mutated (Roquin(san)), Icos is overexpressed in T cells. Here we show that Roquin enhances Dicer-mediated processing of pre-miR-146a. Roquin also directly binds Argonaute2, a central component of the RNA-induced silencing complex, and miR-146a, a microRNA that targets Icos mRNA. In the absence of functional Roquin, miR-146a accumulates in T cells. Its accumulation is not due to increased transcription or processing, rather due to enhanced stability of mature miR-146a. This is associated with decreased 3' end uridylation of the miRNA. Crystallographic studies reveal that Roquin contains a unique HEPN domain and identify the structural basis of the 'san' mutation and Roquin's ability to bind multiple RNAs. Roquin emerges as a protein that can bind Ago2, miRNAs and target mRNAs, to control homeostasis of both RNA species.
Dokumententyp: | Zeitschriftenartikel |
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Fakultät: | Medizin > Institut für Immunologie |
Themengebiete: | 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit |
URN: | urn:nbn:de:bvb:19-epub-34448-3 |
ISSN: | 2041-1723 |
Sprache: | Englisch |
Dokumenten ID: | 34448 |
Datum der Veröffentlichung auf Open Access LMU: | 15. Feb. 2017, 16:04 |
Letzte Änderungen: | 04. Nov. 2020, 13:12 |