Molecular basis for AU-rich element recognition and dimerization by the HuR C-terminal RRM

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F19%3A73597969" target="_blank" >RIV/61989592:15310/19:73597969 - isvavai.cz</a>
Alternative codes found
RIV/68081707:_____/19:00502832
Result on the web
<a href="https://www.pnas.org/content/116/8/2935" target="_blank" >https://www.pnas.org/content/116/8/2935</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1073/pnas.1808696116" target="_blank" >10.1073/pnas.1808696116</a>

Result language
angličtina
Original language name
Molecular basis for AU-rich element recognition and dimerization by the HuR C-terminal RRM
Original language description
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-angstrom-resolution crystal structure of RRM3 bound to different ARE motifs. This structure together with biophysical methods and cellculture 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.
Czech name
—
Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
10403 - Physical chemistry

Project
<a href="/en/project/LO1305" target="_blank" >LO1305: Development of the center of advanced technologies and materials</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN
0027-8424
e-ISSN
—
Volume of the periodical
116
Issue of the periodical within the volume
8
Country of publishing house
US - UNITED STATES
Number of pages
10
Pages from-to
2935-2944
UT code for WoS article
000459074400029
EID of the result in the Scopus database
2-s2.0-85061869822

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