title: Sumoylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding to specific motifs.
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.
authors.affiliation: 1] Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, Madrid 28029, Spain [2] Servicio de Inmunología, Hospital de la Princesa, Madrid 28006, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Villarroya-Beltri
authors.affiliation: Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, Madrid 28029, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Gutiérrez-Vázquez
authors.affiliation: Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, Madrid 28029, Spain.
authors.forename: Fátima
authors.initials: F
authors.lastname: Sánchez-Cabo
authors.affiliation: Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, Madrid 28029, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Pérez-Hernández
authors.affiliation: Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, Madrid 28029, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Vázquez
authors.affiliation: Servicio de Inmunología, Hospital de la Princesa, Madrid 28006, Spain.
authors.forename: Noa
authors.initials: N
authors.lastname: Martin-Cofreces
authors.affiliation: National Center for Biotechnology-CSIC, Madrid 28049, Spain.
authors.forename: Dannys Jorge
authors.initials: DJ
authors.lastname: Martinez-Herrera
authors.affiliation: National Center for Biotechnology-CSIC, Madrid 28049, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Pascual-Montano
authors.affiliation: 1] Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, Madrid 28029, Spain [2].
authors.forename: María
authors.initials: M
authors.lastname: Mittelbrunn
authors.affiliation: 1] Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, Madrid 28029, Spain [2] Servicio de Inmunología, Hospital de la Princesa, Madrid 28006, Spain [3].
authors.forename: Francisco
authors.initials: F
authors.lastname: Sánchez-Madrid
mesh_terms: D020816:Amino Acid Motifs; D002450:Cell Communication; D055354:Exosomes / Q000378:metabolism*; D020868:Gene Silencing; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D035683:MicroRNAs / Q000378:metabolism*; D016296:Mutagenesis; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D011485:Protein Binding; D058207:Sumoylation
chemical_list: D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D035683:MicroRNAs; C439768:hnRNP A2