Pseudo-RNA-Binding Domains Mediate RNA Structure Specificity in Upstream of N-Ras.

Cell Reports
Nele Merret HollmannJanosch Hennig

Abstract

RNA-binding proteins (RBPs) commonly feature multiple RNA-binding domains (RBDs), which provide these proteins with a modular architecture. Accumulating evidence supports that RBP architectural modularity and adaptability define the specificity of their interactions with RNA. However, how multiple RBDs recognize their cognate single-stranded RNA (ssRNA) sequences in concert remains poorly understood. Here, we use Upstream of N-Ras (Unr) as a model system to address this question. Although reported to contain five ssRNA-binding cold-shock domains (CSDs), we demonstrate that Unr includes an additional four CSDs that do not bind RNA (pseudo-RBDs) but are involved in mediating RNA tertiary structure specificity by reducing the conformational heterogeneity of Unr. Disrupting the interactions between canonical and non-canonical CSDs impacts RNA binding, Unr-mediated translation regulation, and the Unr-dependent RNA interactome. Taken together, our studies reveal a new paradigm in protein-RNA recognition, where interactions between RBDs and pseudo-RBDs select RNA tertiary structures, influence RNP assembly, and define target specificity.

References

Nov 1, 1995·Journal of Biomolecular NMR·F DelaglioA Bax
May 23, 1996·Nature·R W HooftE E Abola
Jan 3, 1997·The Journal of Biological Chemistry·W JiangM Inouye
Dec 1, 1996·Journal of Biomolecular NMR·R A LaskowskiJ M Thornton
Apr 2, 1999·Nucleic Acids Research·G TriqueneauxH Jacquemin-Sablon
Mar 24, 2000·Journal of Magnetic Resonance·G ZhuK H Sze
Jan 23, 2003·Bioinformatics·Jens P LingeMichael Nilges
Dec 24, 2003·Protein Science : a Publication of the Protein Society·Narasimha Sreerama, Robert W Woody
Jul 3, 2004·Genes & Development·Katsutomo OkamuraMikiko C Siomi
Jan 22, 2005·The EMBO Journal·Gaynor J BatesFrances V Fuller-Pace
Dec 21, 2005·Molecular Cell·Martin Fenger-GrønJens Lykke-Andersen
Sep 20, 2006·Nucleic Acids Research·Sigrid D AuweterFrédéric H-T Allain
Nov 24, 2006·Bioinformatics·Wolfgang RiepingMichael Nilges
Jan 22, 2008·RNA·Irina Abaza, Fátima Gebauer
May 26, 2009·Acta Crystallographica. Section D, Biological Crystallography·Thomas C TerwilligerLi Wei Hung
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Wolfgang Kabsch
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·P EmsleyK Cowtan
Feb 3, 2011·Current Genomics·Christoph P BagowskiAartjan J W Te Velthuis
Oct 30, 2012·Bioinformatics·Alexander DobinThomas R Gingeras
May 10, 2013·Journal of Biomolecular NMR·Alexandra AhlnerPatrik Lundström
Jun 12, 2013·Annual Review of Biochemistry·Rebecca M Voorhees, V Ramakrishnan
Jun 15, 2013·Journal of Synchrotron Radiation·Petra PernotSean McSweeney
Jun 22, 2013·Genes & Development·Antoine GraindorgeFátima Gebauer
Aug 22, 2013·Progress in Nuclear Magnetic Resonance Spectroscopy·Mike P Williamson

❮ Previous
Next ❯

Citations

Feb 14, 2021·Drug Discovery Today·Christian Bailly, Gérard Vergoten
Apr 10, 2021·Oncogene·Pavan Kumar KakumaniMartin J Simard

❮ Previous
Next ❯

Methods Mentioned

BETA
RIP-seq
immunoprecipitation
NMR
X-ray
N
circular dichroism
transfection
pull-downs
pull-down
immunoprecipitation assay

Software Mentioned

PyMOL
PROCHECK
PINT
ENSEMBL
ESPript
Gnuplot
CRYSOL
VennDiagram
NMRPipe
SELCON3

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.