Structural insight into the mechanism of stabilization of the 7SK small nuclear RNA by LARP7

Nucleic Acids Research
Emiko UchikawaAnne-Catherine Dock-Bregeon

Abstract

The non-coding RNA 7SK is the scaffold for a small nuclear ribonucleoprotein (7SKsnRNP) which regulates the function of the positive transcription elongation factor P-TEFb in the control of RNA polymerase II elongation in metazoans. The La-related protein LARP7 is a component of the 7SKsnRNP required for stability and function of the RNA. To address the function of LARP7 we determined the crystal structure of its La module, which binds a stretch of uridines at the 3'-end of 7SK. The structure shows that the penultimate uridine is tethered by the two domains, the La-motif and the RNA-recognition motif (RRM1), and reveals that the RRM1 is significantly smaller and more exposed than in the La protein. Sequence analysis suggests that this impacts interaction with 7SK. Binding assays, footprinting and small-angle scattering experiments show that a second RRM domain located at the C-terminus binds the apical loop of the 3' hairpin of 7SK, while the N-terminal domains bind at its foot. Our results suggest that LARP7 uses both its N- and C-terminal domains to stabilize 7SK in a closed structure, which forms by joining conserved sequences at the 5'-end with the foot of the 3' hairpin and has thus functional implications.

References

Nov 25, 1987·Nucleic Acids Research·C EhresmannB Ehresmann
May 26, 1995·The Journal of Biological Chemistry·N F Marshall, D H Price
Oct 3, 1998·Acta Crystallographica. Section D, Biological Crystallography·A T BrüngerG L Warren
May 13, 1999·Bioinformatics·P GouetF Métoz
May 24, 2001·Biophysical Journal·D I SvergunM H Koch
Jun 26, 2003·Nucleic Acids Research·Michael Zuker
Jul 2, 2003·Molecular and Cellular Biology·Annemieke A MichelsOlivier Bensaude
Jul 31, 2003·Nucleic Acids Research·Scott C WalkerGraeme L Conn
Mar 9, 2004·Nature Structural & Molecular Biology·Caterina AlfanoMaria R Conte
Mar 23, 2004·Nucleic Acids Research·Robert C Edgar
May 8, 2004·Genes & Development·Keren L Witkin, Kathleen Collins
Jun 18, 2004·The EMBO Journal·Annemieke A MichelsOlivier Bensaude
Jun 25, 2004·Nucleic Acids Research·Matthias Heinig, Dmitrij Frishman
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Jun 1, 2005·Biophysical Journal·Maxim V Petoukhov, Dmitri I Svergun
Dec 22, 2005·Acta Crystallographica. Section D, Biological Crystallography·Philip Evans
Jan 24, 2006·Molecular Cell·Richard J Maraia, Mark A Bayfield
Aug 4, 2006·Molecular Cell·B Matija Peterlin, David H Price
Sep 12, 2006·Analytical Biochemistry·Ulrika B EricssonPär Nordlund
Dec 14, 2006·Acta Crystallographica. Section D, Biological Crystallography·Airlie J McCoy
Jul 6, 2007·The EMBO Journal·Elodie Van HerrewegheTamás Kiss
Nov 17, 2007·Nature Protocols·Axel T Brunger
Mar 7, 2008·Nature·Marc Parisien, François Major
Jun 21, 2008·Molecular Biology and Evolution·Andreas R GruberPeter F Stadler
Feb 28, 2009·RNA Biology·Gaelle Diribarne, Olivier Bensaude
Mar 21, 2009·RNA·Cécile Bousquet-Antonelli, Jean-Marc Deragon
Aug 1, 2007·Journal of Applied Crystallography·Airlie J McCoyRandy J Read
Sep 8, 2009·Molecular Biology and Evolution·Manja MarzOlivier Bensaude
Feb 9, 2010·Biochimica Et Biophysica Acta·Mark A BayfieldRichard J Maraia
Jun 11, 2010·Nature·Tahir H TahirovDavid H Price
Aug 3, 2010·Nucleic Acids Research·Isabelle LebarsAnne-Catherine Dock-Bregeon

❮ Previous
Next ❯

Citations

Oct 27, 2015·Biomolecules·Chara Stavraka, Sarah Blagden
Sep 2, 2015·Biochimica Et Biophysica Acta·Amanda J BlytheCharles S Bond
Apr 12, 2015·Biochimie·Denise Martinez-ZapienAnne-Catherine Dock-Bregeon
Jul 3, 2016·Nucleic Acids Research·Alexandre J C QuaresmaMatjaz Barboric
Sep 30, 2016·Nucleic Acids Research·Catherine D EichhornJuli Feigon
May 10, 2017·The Journal of Clinical Investigation·Kamaleldin E ElagibAdam N Goldfarb
Feb 16, 2018·Nucleic Acids Research·Jyotsna VinayakMark A Bayfield
Aug 7, 2017·Wiley Interdisciplinary Reviews. RNA·Richard J MaraiaMaria R Conte
Feb 10, 2018·Nature Communications·Laura C CollopyKazunori Tomita
Feb 10, 2018·Nature Communications·Amanda K MennieToru M Nakamura
Dec 9, 2017·RNA Biology·Ali M YazbeckPeter F Stadler
Nov 17, 2019·Nucleic Acids Research·Konstantin RöderSamuela Pasquali
Oct 28, 2019·Journal of Human Genetics·Ivan IvanovskiLivia Garavelli
Mar 19, 2020·RNA Biology·Javier LizarrondoMaria R Conte
May 14, 2020·RNA Biology·Daniele HaslerUtz Fischer
Jun 28, 2018·Proceedings of the National Academy of Sciences of the United States of America·Catherine D EichhornJuli Feigon
Dec 19, 2018·Nature Chemical Biology·Yuan YangJuli Feigon
Jan 14, 2017·Nucleic Acids Research·Denise Martinez-ZapienAnne-Catherine Dock-Bregeon
Jan 12, 2019·Biomolecular NMR Assignments·Isabel Cruz-GallardoMaria R Conte
Apr 22, 2017·Nucleic Acids Research·John E Brogie, David H Price
Oct 12, 2019·RNA Biology·Hiba A Al-AshtalAndrea J Berman
Feb 2, 2021·RNA Biology·Sandy MattijssenRichard J Maraia
Sep 1, 2021·BMC Molecular and Cell Biology·Duy NguyenPatricia Uguen

❮ Previous
Next ❯

Methods Mentioned

BETA
footprinting
X-ray
in vitro transcription
electrophoretic mobility shift
electrophoretic mobility shift assay
amputation

Software Mentioned

Fold
SASREF
ClustalOmega
BLAST
BUSTER
HsLa
PRIMUS
MOSFLM
FOXTROT
CRYSOL

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.