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dc.contributor.author
Ripin, Nina
dc.contributor.author
Boudet, Julien
dc.contributor.author
Duszczyk, Malgorzata M.
dc.contributor.author
Hinniger, Alexandra
dc.contributor.author
Faller, Michael
dc.contributor.author
Krepl, Miroslav
dc.contributor.author
Gadi, Abhilash
dc.contributor.author
Schneider, Robert J.
dc.contributor.author
Šponer, Jiří
dc.contributor.author
Meisner‐Kober, Nicole
dc.contributor.author
Allain, Frédéric H.-T.
dc.date.accessioned
2019-03-01T17:03:08Z
dc.date.available
2019-03-01T05:16:34Z
dc.date.available
2019-03-01T17:03:08Z
dc.date.issued
2019-02-19
dc.identifier.issn
0027-8424
dc.identifier.issn
1091-6490
dc.identifier.other
10.1073/pnas.1808696116
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/328390
dc.identifier.doi
10.3929/ethz-b-000328390
dc.description.abstract
Human antigen R (HuR) is a key regulator of cellular mRNAs containing adenylate/uridylate–rich elements (AU-rich elements; AREs). These are a major class of cis elements within 3′ untranslated regions, targeting these mRNAs for rapid degradation. HuR contains three RNA recognition motifs (RRMs): a tandem RRM1 and 2, followed by a flexible linker and a C-terminal RRM3. While RRM1 and 2 are structurally characterized, little is known about RRM3. Here we present a 1.9-Å-resolution crystal structure of RRM3 bound to different ARE motifs. This structure together with biophysical methods and cell-culture assays revealed the mechanism of RRM3 ARE recognition and dimerization. While multiple RNA motifs can be bound, recognition of the canonical AUUUA pentameric motif is possible by binding to two registers. Additionally, RRM3 forms homodimers to increase its RNA binding affinity. Finally, although HuR stabilizes ARE-containing RNAs, we found that RRM3 counteracts this effect, as shown in a cell-based ARE reporter assay and by qPCR with native HuR mRNA targets containing multiple AUUUA motifs, possibly by competing with RRM12.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
National Academy of Sciences
en_US
dc.rights.uri
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject
NMR spectroscopy
en_US
dc.subject
Crystal structure
en_US
dc.subject
RNA-binding protein
en_US
dc.subject
Dimerization
en_US
dc.subject
multiple register
en_US
dc.title
Molecular basis for AU-rich element recognition and dimerization by the HuR C-terminal RRM
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
ethz.journal.title
Proceedings of the National Academy of Sciences of the United States of America
ethz.journal.volume
116
en_US
ethz.journal.issue
8
en_US
ethz.journal.abbreviated
PNAS
ethz.pages.start
2935
en_US
ethz.pages.end
2944
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
Washington, DC
en_US
ethz.publication.status
published
en_US
ethz.date.deposited
2019-03-01T05:16:37Z
ethz.source
SCOPUS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2019-03-01T17:03:15Z
ethz.rosetta.lastUpdated
2019-03-01T17:03:15Z
ethz.rosetta.exportRequired
true
ethz.rosetta.versionExported
true
ethz.COinS
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