TY - JOUR
T1 - Sumoylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding to specific motifs
AU - Villarroya-Beltri, Carolina
AU - Gutiérrez-Vázquez, Cristina
AU - Sánchez-Cabo, Fátima
AU - Pérez-Hernández, Daniel
AU - Vázquez, Jesús
AU - Martin-Cofreces, Noa
AU - Martinez-Herrera, Dannys Jorge
AU - Pascual-Montano, Alberto
AU - Mittelbrunn, María
AU - Sánchez-Madrid, Francisco
N1 - Funding Information:
We thank Dr A. Ramiro, Dr G. Bossis and Dr M. Blasco for providing reagents. We are grateful to Dr S. Bartlett for assistance with English editing and F. Baixauli for helpful discussions. We also thank the CNIC Genomics and Bioinformatics Units for technical support. FACS analysis and sorting were conducted at the CNIC Cellomics Unit. 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 Caixa.
PY - 2013/12/20
Y1 - 2013/12/20
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84890907806&partnerID=8YFLogxK
U2 - 10.1038/ncomms3980
DO - 10.1038/ncomms3980
M3 - Article
C2 - 24356509
AN - SCOPUS:84890907806
SN - 2041-1723
VL - 4
JO - Nature Communications
JF - Nature Communications
M1 - 2980
ER -