Format

Send to

Choose Destination
Nucleic Acids Res. 2018 Oct 8. doi: 10.1093/nar/gky908. [Epub ahead of print]

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

Author information

1
Department of Biology, Technische Universität Darmstadt, Darmstadt 64287, Germany.
2
Department of Biochemistry and Biophysics and Center for RNA Biology, University of Rochester Medical Center, Rochester, NY 14642, USA.
3
Biophysical Mass Spectrometry Group, Max Planck Institute for Biophysical Chemistry, Göttingen 37077, Germany.
4
Bioanalytics, Institute for Clinical Chemistry, University Medical Center, 37073 Göttingen, Germany.

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.

PMID:
30295819
DOI:
10.1093/nar/gky908

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center