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

Autor: Essig, Katharina, Kronbeck, Nina, Guimaraes, Joao C., Lohs, Claudia, Schlundt, Andreas, Hoffmann, Anne, Behrens, Gesine, Brenner, Sven, Kowalska, Joanna, Lopez-Rodriguez, Cristina, Jemielity, Jacek, Holtmann, Helmut, Reiche, Kristin, Hackermüller, Jörg, Sattler, Michael, Zavolan, Mihaela, Heissmeyer, Vigo
Zdroj: Nature Communications; 9/19/2018, Vol. 9 Issue 1, p1-1, 1p
Abstrakt: 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. Roquin targets are known to contain two types of sequence-structure motifs, the constitutive and the alternative decay elements (CDE and ADE). Here, the authors describe a linear Roquin binding element (LBE) also involved in target recognition, and show that Roquin binding affects the translation of a subset of targeted mRNAs. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index