A cryptic RNA-binding domain mediates Syncrip recognition and exosomal partitioning of miRNA targets.

Nature Communications
Fruzsina HoborAndres Ramos

Abstract

Exosomal miRNA transfer is a mechanism for cell-cell communication that is important in the immune response, in the functioning of the nervous system and in cancer. Syncrip/hnRNPQ is a highly conserved RNA-binding protein that mediates the exosomal partition of a set of miRNAs. Here, we report that Syncrip's amino-terminal domain, which was previously thought to mediate protein-protein interactions, is a cryptic, conserved and sequence-specific RNA-binding domain, designated NURR (N-terminal unit for RNA recognition). The NURR domain mediates the specific recognition of a short hEXO sequence defining Syncrip exosomal miRNA targets, and is coupled by a non-canonical structural element to Syncrip's RRM domains to achieve high-affinity miRNA binding. As a consequence, Syncrip-mediated selection of the target miRNAs implies both recognition of the hEXO sequence by the NURR domain and binding of the RRM domains 5' to this sequence. This structural arrangement enables Syncrip-mediated selection of miRNAs with different seed sequences.

References

Nov 1, 1995·Journal of Biomolecular NMR·F DelaglioA Bax
Aug 31, 2000·Journal of Molecular Biology·C NotredameJ Heringa
Sep 28, 2001·The EMBO Journal·Z MourelatosG Dreyfuss
May 1, 1997·Acta Crystallographica. Section D, Biological Crystallography·G N MurshudovE J Dodson
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Nov 23, 2005·Bioinformatics·Konstantin ArnoldTorsten Schwede
Oct 3, 2006·Biochemical and Biophysical Research Communications·Alexandre J C QuaresmaJörg Kobarg
May 3, 2007·Nature Reviews. Molecular Cell Biology·Bradley M LundeGabriele Varani
Jun 15, 2007·Nature Structural & Molecular Biology·Sonia Guil, Javier F Cáceres
Jul 28, 2007·Journal of the American Chemical Society·Barbara BeuthAndres Ramos
Jun 11, 2008·Methods in Molecular Biology·Peter H ZwartPaul D Adams
Jan 20, 2009·Bioinformatics·Andrew M WaterhouseGeoffrey J Barton
Aug 1, 2007·Journal of Applied Crystallography·Airlie J McCoyRandy J Read
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Wolfgang Kabsch
May 1, 2010·Nature Protocols·Sjoerd J de VriesAlexandre M J J Bonvin
Apr 21, 2011·Nature Communications·María MittelbrunnFrancisco Sánchez-Madrid
Mar 1, 2012·Nucleic Acids Research·Pradipta KunduWitold Filipowicz
Feb 1, 2013·The Journal of Biological Chemistry·Lydie MorelYongjie Yang
Apr 27, 2013·The Journal of Clinical Investigation·Julie HalkeinIngrid Struman
Dec 21, 2013·Nature Communications·Carolina Villarroya-BeltriFrancisco Sánchez-Madrid
May 23, 2014·Antioxidants & Redox Signaling·Laura KuchlerAndreas von Knethen
Jan 15, 2015·Nucleic Acids Research·Katherine M CollinsAndres Ramos
Sep 28, 2015·Journal of Molecular Biology·G C P van ZundertA M J J Bonvin
Dec 15, 2015·Molecular Biology of the Cell·Kathryn R WilliamsGary J Bassell
Dec 19, 2015·PLoS Computational Biology·Zhichao Miao, Eric Westhof
Feb 20, 2016·Nature Reviews. Neuroscience·Vivian BudnikFranz Wendler
Apr 16, 2016·Protein Science : a Publication of the Protein Society·Christine BeuckPedro Serrano
Jul 13, 2016·EMBO Reports·Kamalika MukherjeeSuvendra N Bhattacharyya
Jul 28, 2016·Molecular Cell·Alfredo CastelloMatthias W Hentze

❮ Previous
Next ❯

Citations

Aug 11, 2020·Cell Communication and Signaling : CCS·Xueqiang PengHangyu Li
Jun 2, 2018·FEBS Letters·Christopher Gallagher, Andres Ramos
Apr 10, 2019·Wiley Interdisciplinary Reviews. RNA·Sarah ResselAmy H Buck
Aug 5, 2020·Acta Neuropathologica·Alexander BamptonAriana Gatt
Dec 29, 2018·Journal of Clinical Medicine·Alice Conigliaro, Carla Cicchini
Oct 31, 2019·FEBS Letters·Katiuska González-ArzolaMiguel Á De la Rosa
Jan 8, 2020·RNA·Ying ChenChacko Jobichen
Oct 17, 2019·International Journal of Molecular Sciences·Andrea CaccioppoMaria Felice Brizzi
May 28, 2020·Nature Reviews. Molecular Cell Biology·Killian O'BrienXandra O Breakefield
Mar 29, 2019·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Rosario Francisco-VelillaEncarnacion Martinez-Salas
Dec 8, 2020·Frontiers in Cellular Neuroscience·Forrest WeghorstKarina S Cramer
Dec 21, 2019·Cancer Immunology Research·Virginie VignardDelphine Fradin
Oct 9, 2020·RNA Biology·Sharof KhudayberdievGerhard Schratt
Jan 14, 2021·Advanced Science·Fei Teng, Martin Fussenegger
Apr 20, 2021·Journal of Experimental Botany·Ayako OkuzakiChristian Schmitz-Linneweber
Sep 21, 2021·Immunological Reviews·Grant K NationHeather H Pua
Dec 4, 2019·Biochemical and Biophysical Research Communications·Yuan HeJianxing Song
Nov 11, 2021·Journal of Leukocyte Biology·Mrigya Babuta, Gyongyi Szabo
Oct 28, 2021·Advanced Healthcare Materials·Bryan Z WangGordana Vunjak-Novakovic
Sep 4, 2020·Molecular Therapy : the Journal of the American Society of Gene Therapy·Ping SunJiawei Tian

❮ Previous
Next ❯

Methods Mentioned

BETA
X-ray
nuclear magnetic resonance
NMR
biolayer interferometry
RNA-immunoprecipitation
RIP
pulldown
pull down
size exclusion chromatography
gel filtration

Software Mentioned

PHENIX
TLSMD
SWISS
PyMol
HADDOCK
PALES
CARA
COOT
PyMOL Molecular Graphics System
Jalview

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.