Sumoylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding to specific motifs
Entity
UAM. Departamento de MedicinaPublisher
Nature Publishung GroupDate
2013-12-20Citation
10.1038/ncomms3980
Nature Communications 4 (2013): 2980
ISSN
2041-1723DOI
10.1038/ncomms3980Funded by
This work was supported by grants SAF2011-25834, ERC-2011-AdG, BIO2009_07990, BIO2010-17527, COST-Action BM1202, P210/BMD-2305 and Cardiovascular Network RD12-0042-0056 from Instituto Salud Carlos III. C.V.B. was supported by FPU program (Spanish Ministry of Education). M.M. was supported by the Instituto de Salud Carlos III, C.G.-V. by the Comunidad de Madrid and D.J.M.H. by Programa La CaixaProject
Comunidad de Madrid. S2010/BMD-2332/INDISNET; Comunidad de Madrid. S2010/BMD-2305/CS INTERACTOMICSSubjects
Exosomes; MicroRNAs; Mutagenesis; Sumoylation; MedicinaRights
© 2013 Macmillan Publishers LimitedEsta obra está bajo una licencia de Creative Commons Reconocimiento-NoComercial-SinObraDerivada 4.0 Internacional.
Abstract
Exosomes are released by most cells to the extracellular environment and are involved in cell-to-cell communication. Exosomes contain specific repertoires of mRNAs, microRNAs (miRNAs) and other non-coding RNAs that can be functionally transferred to recipient cells. However, the mechanisms that control the specific loading of RNA species into exosomes remain unknown. Here we describe sequence motifs present in miRNAs that control their localization into exosomes. The protein heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) specifically binds exosomal miRNAs through the recognition of these motifs and controls their loading into exosomes. Moreover, hnRNPA2B1 in exosomes is sumoylated, and sumoylation controls the binding of hnRNPA2B1 to miRNAs. The loading of miRNAs into exosomes can be modulated by mutagenesis of the identified motifs or changes in hnRNPA2B1 expression levels. These findings identify hnRNPA2B1 as a key player in miRNA sorting into exosomes and provide potential tools for the packaging of selected regulatory RNAs into exosomes and their use in biomedical applications
Files in this item
Google Scholar:Villarroya Beltri, Carolina
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Gutiérrez-Vázquez, Cristina
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Sánchez-Cabo, Fátima
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Pérez-Hernández, Daniel
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Vázquez, Jesús
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Martín-Cófreces, Noa
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Martínez-Herrera, Dannys Jorge
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Pascual-Montano, Alberto
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Mittelbrum Herrero, María
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Sánchez Madrid, Francisco
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- Producción científica de la UAM [20543]
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