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

Essig, Katharina and Kronbeck, Nina and Guimaraes, Joao C. and Lohs, Claudia and Schlundt, Andreas and Hoffmann, Anne and Behrens, Gesine and Brenner, Sven and Kowalska, Joanna and Lopez-Rodriguez, Cristina and Jemielity, Jacek and Holtmann, Helmut and Reiche, Kristin and Hackermüller, Jörg and Sattler, Michael and Zavolan, Mihaela and Heissmeyer, Vigo. (2018) Roquin targets mRNAs in a 3'-UTR-specific manner by different modes of regulation. Nature communications, 9 (1). p. 3810.

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Official URL: https://edoc.unibas.ch/66718/

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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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Computational & Systems Biology > Bioinformatics (Zavolan)
UniBasel Contributors:Zavolan, Mihaela and Azevedo Salgado Guimaraes, Joao Carlos
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:26 Apr 2020 19:20
Deposited On:26 Apr 2020 19:20

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