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Identification of new high affinity targets for Roquin based on structural conservation

Braun, Johannes and Fischer, Sandra and Xu, Zhenjiang Z. and Sun, Hongying and Ghoneim, Dalia H. and Gimbel, Anna T. and Plessmann, Uwe and Urlaub, Henning and Mathews, David H. and Weigand, Julia E. (2018):
Identification of new high affinity targets for Roquin based on structural conservation.
In: Nucleic acids research, 46 (22), pp. 12109-12125. Oxford University Press, ISSN 1362-4962,
DOI: 10.1093/nar/gky908,
[Article]

Abstract

Post-transcriptional gene regulation controls the amount of protein produced from a specific mRNA by altering both its decay and translation rates. Such regulation is primarily achieved by the interaction of trans-acting factors with cis-regulatory elements in the untranslated regions (UTRs) of mRNAs. These interactions are guided either by sequence- or structure-based recognition. Similar to sequence conservation, the evolutionary conservation of a UTR's structure thus reflects its functional importance. We used such structural conservation to identify previously unknown cis-regulatory elements. Using the RNA folding program Dynalign, we scanned all UTRs of humans and mice for conserved structures. Characterizing a subset of putative conserved structures revealed a binding site of the RNA-binding protein Roquin. Detailed functional characterization in vivo enabled us to redefine the binding preferences of Roquin and identify new target genes. Many of these new targets are unrelated to the established role of Roquin in inflammation and immune responses and thus highlight additional, unstudied cellular functions of this important repressor. Moreover, the expression of several Roquin targets is highly cell-type-specific. In consequence, these targets are difficult to detect using methods dependent on mRNA abundance, yet easily detectable with our unbiased strategy.

Item Type: Article
Erschienen: 2018
Creators: Braun, Johannes and Fischer, Sandra and Xu, Zhenjiang Z. and Sun, Hongying and Ghoneim, Dalia H. and Gimbel, Anna T. and Plessmann, Uwe and Urlaub, Henning and Mathews, David H. and Weigand, Julia E.
Title: Identification of new high affinity targets for Roquin based on structural conservation
Language: English
Abstract:

Post-transcriptional gene regulation controls the amount of protein produced from a specific mRNA by altering both its decay and translation rates. Such regulation is primarily achieved by the interaction of trans-acting factors with cis-regulatory elements in the untranslated regions (UTRs) of mRNAs. These interactions are guided either by sequence- or structure-based recognition. Similar to sequence conservation, the evolutionary conservation of a UTR's structure thus reflects its functional importance. We used such structural conservation to identify previously unknown cis-regulatory elements. Using the RNA folding program Dynalign, we scanned all UTRs of humans and mice for conserved structures. Characterizing a subset of putative conserved structures revealed a binding site of the RNA-binding protein Roquin. Detailed functional characterization in vivo enabled us to redefine the binding preferences of Roquin and identify new target genes. Many of these new targets are unrelated to the established role of Roquin in inflammation and immune responses and thus highlight additional, unstudied cellular functions of this important repressor. Moreover, the expression of several Roquin targets is highly cell-type-specific. In consequence, these targets are difficult to detect using methods dependent on mRNA abundance, yet easily detectable with our unbiased strategy.

Journal or Publication Title: Nucleic acids research
Journal volume: 46
Number: 22
Publisher: Oxford University Press
Divisions: 10 Department of Biology
10 Department of Biology > RNA Biochemistry
Date Deposited: 05 Mar 2021 07:54
DOI: 10.1093/nar/gky908
Official URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6294493/
Identification Number: pmid:30295819
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