Roquin targets mRNAs in a 3′-UTR-specific manner by different modes of regulation

Essig, Katharina; Kronbeck, Nina; Guimaraes, Joao C.; Lohs, Claudia; Schlundt, Andreas; Hoffmann, Anne; Behrens, Gesine; Brenner, Sven; Kowalska, Joanna; López Rodríguez, M. Cristina; Jemielity, Jacek; Holtmann, Helmut; Reiche, Kristin; Hackermüller, Jörg; Sattler, Michael; Zavolan, Mihaela; Heissmeyer, Vigo

doi:http://dx.doi.org/10.1038/s41467-018-06184-3

Roquin targets mRNAs in a 3′-UTR-specific manner by different modes of regulation

Citation

Essig 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/s41467-018-06184-3

Abstract

The 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.