Essig, KatharinaKronbeck, NinaGuimaraes, Joao C.Lohs, ClaudiaSchlundt, AndreasHoffmann, AnneBehrens, GesineBrenner, SvenKowalska, JoannaLópez Rodríguez, M. CristinaJemielity, JacekHoltmann, HelmutReiche, KristinHackermüller, JörgSattler, MichaelZavolan, MihaelaHeissmeyer, Vigo2019-04-042019-04-042018Essig K, Kronbeck N, Guimaraes JC, Lohs C, Schlundt A, Hoffmann A et al. Roquin targets mRNAs in a 3′-UTR-specific manner by different modes of regulation. Nat Commun. 2018;9(1):3810. DOI: 10.1038/s41467-018-06184-32041-1723http://hdl.handle.net/10230/37038The RNA-binding proteins Roquin-1 and Roquin-2 redundantly control gene expression and cell-fate decisions. Here, we show that Roquin not only interacts with stem-loop structures, but also with a linear sequence element present in about half of its targets. Comprehensive analysis of a minimal response element of the Nfkbid 3'-UTR shows that six stem-loop structures cooperate to exert robust and profound post-transcriptional regulation. Only binding of multiple Roquin proteins to several stem-loops exerts full repression, which redundantly involved deadenylation and decapping, but also translational inhibition. Globally, most Roquin targets are regulated by mRNA decay, whereas a small subset, including the Nfat5 mRNA, with more binding sites in their 3'-UTRs, are also subject to translational inhibition. These findings provide insights into how the robustness and magnitude of Roquin-mediated regulation is encoded in complex cis-elements.application/pdfeng© The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41467-018-06184-3AutoimmunityRNA decayRNA foldingTranslationinfo:eu-repo/semantics/openAccess