-
Je něco špatně v tomto záznamu ?
Molecular basis for AU-rich element recognition and dimerization by the HuR C-terminal RRM
N. Ripin, J. Boudet, MM. Duszczyk, A. Hinniger, M. Faller, M. Krepl, A. Gadi, RJ. Schneider, J. Šponer, NC. Meisner-Kober, FH. Allain,
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, práce podpořená grantem
NLK
Free Medical Journals
od 1915 do Před 6 měsíci
Freely Accessible Science Journals
od 1915 do Před 6 měsíci
PubMed Central
od 1915 do Před 6 měsíci
Europe PubMed Central
od 1915 do Před 6 měsíci
Open Access Digital Library
od 1915-01-15
Open Access Digital Library
od 1915-01-01
PubMed
30718402
DOI
10.1073/pnas.1808696116
Knihovny.cz E-zdroje
- MeSH
- 3' nepřekládaná oblast MeSH
- dimerizace MeSH
- encefalomyelitida paraneoplastická - Hu antigeny chemie MeSH
- HuR protein chemie genetika MeSH
- krystalografie rentgenová MeSH
- lidé MeSH
- magnetická rezonanční spektroskopie MeSH
- motiv rozpoznávající RNA genetika MeSH
- nádorové supresorové proteiny chemie MeSH
- proteiny vázající RNA chemie genetika MeSH
- ribonukleosiddifosfátreduktasa chemie MeSH
- úseky bohaté na AU genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
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.
Department of Microbiology New York University School of Medicine New York NY 10016
Novartis Institutes for BioMedical Research 4002 Basel Switzerland
- 000
- 00000naa a2200000 a 4500
- 001
- bmc19027852
- 003
- CZ-PrNML
- 005
- 20190815112746.0
- 007
- ta
- 008
- 190813s2019 xxu f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1073/pnas.1808696116 $2 doi
- 035 __
- $a (PubMed)30718402
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a xxu
- 100 1_
- $a Ripin, Nina $u Department of Biology, Institute of Molecular Biology and Biophysics, ETH Zürich, 8093 Zürich, Switzerland; nina.ripin@mol.biol.ethz.ch nicole.meisner-kober@sbg.ac.at frederic.allain@mol.biol.ethz.ch. Novartis Institutes for BioMedical Research, 4002 Basel, Switzerland.
- 245 10
- $a Molecular basis for AU-rich element recognition and dimerization by the HuR C-terminal RRM / $c N. Ripin, J. Boudet, MM. Duszczyk, A. Hinniger, M. Faller, M. Krepl, A. Gadi, RJ. Schneider, J. Šponer, NC. Meisner-Kober, FH. Allain,
- 520 9_
- $a 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.
- 650 _2
- $a 3' nepřekládaná oblast $7 D020413
- 650 _2
- $a úseky bohaté na AU $x genetika $7 D063307
- 650 _2
- $a krystalografie rentgenová $7 D018360
- 650 _2
- $a dimerizace $7 D019281
- 650 _2
- $a encefalomyelitida paraneoplastická - Hu antigeny $x chemie $7 D051959
- 650 _2
- $a HuR protein $x chemie $x genetika $7 D000067780
- 650 _2
- $a lidé $7 D006801
- 650 _2
- $a magnetická rezonanční spektroskopie $7 D009682
- 650 _2
- $a motiv rozpoznávající RNA $x genetika $7 D000071377
- 650 _2
- $a proteiny vázající RNA $x chemie $x genetika $7 D016601
- 650 _2
- $a ribonukleosiddifosfátreduktasa $x chemie $7 D012262
- 650 _2
- $a nádorové supresorové proteiny $x chemie $7 D025521
- 655 _2
- $a časopisecké články $7 D016428
- 655 _2
- $a práce podpořená grantem $7 D013485
- 700 1_
- $a Boudet, Julien $u Department of Biology, Institute of Molecular Biology and Biophysics, ETH Zürich, 8093 Zürich, Switzerland.
- 700 1_
- $a Duszczyk, Malgorzata M $u Department of Biology, Institute of Molecular Biology and Biophysics, ETH Zürich, 8093 Zürich, Switzerland.
- 700 1_
- $a Hinniger, Alexandra $u Novartis Institutes for BioMedical Research, 4002 Basel, Switzerland.
- 700 1_
- $a Faller, Michael $u Novartis Institutes for BioMedical Research, 4002 Basel, Switzerland.
- 700 1_
- $a Krepl, Miroslav $u Institute of Biophysics, Czech Academy of Sciences, 612 65 Brno, Czech Republic. Department of Physical Chemistry, Faculty of Science, Regional Centre of Advanced Technologies and Materials, Palacky University Olomouc, 771 46 Olomouc, Czech Republic.
- 700 1_
- $a Gadi, Abhilash $u Department of Microbiology, New York University School of Medicine, New York, NY 10016.
- 700 1_
- $a Schneider, Robert J $u Department of Microbiology, New York University School of Medicine, New York, NY 10016.
- 700 1_
- $a Šponer, Jiří $u Institute of Biophysics, Czech Academy of Sciences, 612 65 Brno, Czech Republic. Department of Physical Chemistry, Faculty of Science, Regional Centre of Advanced Technologies and Materials, Palacky University Olomouc, 771 46 Olomouc, Czech Republic.
- 700 1_
- $a Meisner-Kober, Nicole C $u Novartis Institutes for BioMedical Research, 4002 Basel, Switzerland; nina.ripin@mol.biol.ethz.ch nicole.meisner-kober@sbg.ac.at frederic.allain@mol.biol.ethz.ch.
- 700 1_
- $a Allain, Frédéric H-T $u Department of Biology, Institute of Molecular Biology and Biophysics, ETH Zürich, 8093 Zürich, Switzerland; nina.ripin@mol.biol.ethz.ch nicole.meisner-kober@sbg.ac.at frederic.allain@mol.biol.ethz.ch.
- 773 0_
- $w MED00010472 $t Proceedings of the National Academy of Sciences of the United States of America $x 1091-6490 $g Roč. 116, č. 8 (2019), s. 2935-2944
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/30718402 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y a $z 0
- 990 __
- $a 20190813 $b ABA008
- 991 __
- $a 20190815113013 $b ABA008
- 999 __
- $a ok $b bmc $g 1433001 $s 1066312
- BAS __
- $a 3
- BAS __
- $a PreBMC
- BMC __
- $a 2019 $b 116 $c 8 $d 2935-2944 $e 20190204 $i 1091-6490 $m Proceedings of the National Academy of Sciences of the United States of America $n Proc Natl Acad Sci U S A $x MED00010472
- LZP __
- $a Pubmed-20190813