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

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 respon...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6145892/
https://www.ncbi.nlm.nih.gov/pubmed/30232334
http://dx.doi.org/10.1038/s41467-018-06184-3
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author 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
author_facet 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
author_sort Essig, Katharina
collection PubMed
description 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.
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spelling pubmed-61458922018-09-24 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 Lopez-Rodriguez, Cristina Jemielity, Jacek Holtmann, Helmut Reiche, Kristin Hackermüller, Jörg Sattler, Michael Zavolan, Mihaela Heissmeyer, Vigo Nat Commun Article 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. Nature Publishing Group UK 2018-09-19 /pmc/articles/PMC6145892/ /pubmed/30232334 http://dx.doi.org/10.1038/s41467-018-06184-3 Text en © 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/.
spellingShingle Article
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
Roquin targets mRNAs in a 3′-UTR-specific manner by different modes of regulation
title Roquin targets mRNAs in a 3′-UTR-specific manner by different modes of regulation
title_full Roquin targets mRNAs in a 3′-UTR-specific manner by different modes of regulation
title_fullStr Roquin targets mRNAs in a 3′-UTR-specific manner by different modes of regulation
title_full_unstemmed Roquin targets mRNAs in a 3′-UTR-specific manner by different modes of regulation
title_short Roquin targets mRNAs in a 3′-UTR-specific manner by different modes of regulation
title_sort roquin targets mrnas in a 3′-utr-specific manner by different modes of regulation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6145892/
https://www.ncbi.nlm.nih.gov/pubmed/30232334
http://dx.doi.org/10.1038/s41467-018-06184-3
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