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Sumoylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding to specific motifs

Author

Listed:
  • Carolina Villarroya-Beltri

    (Centro Nacional de Investigaciones Cardiovasculares
    Servicio de Inmunología, Hospital de la Princesa)

  • Cristina Gutiérrez-Vázquez

    (Centro Nacional de Investigaciones Cardiovasculares)

  • Fátima Sánchez-Cabo

    (Centro Nacional de Investigaciones Cardiovasculares)

  • Daniel Pérez-Hernández

    (Centro Nacional de Investigaciones Cardiovasculares)

  • Jesús Vázquez

    (Centro Nacional de Investigaciones Cardiovasculares)

  • Noa Martin-Cofreces

    (Servicio de Inmunología, Hospital de la Princesa)

  • Dannys Jorge Martinez-Herrera

    (National Center for Biotechnology-CSIC)

  • Alberto Pascual-Montano

    (National Center for Biotechnology-CSIC)

  • María Mittelbrunn

    (Centro Nacional de Investigaciones Cardiovasculares)

  • Francisco Sánchez-Madrid

    (Centro Nacional de Investigaciones Cardiovasculares
    Servicio de Inmunología, Hospital de la Princesa)

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.

Suggested Citation

  • Carolina Villarroya-Beltri & Cristina Gutiérrez-Vázquez & Fátima Sánchez-Cabo & Daniel Pérez-Hernández & Jesús Vázquez & Noa Martin-Cofreces & Dannys Jorge Martinez-Herrera & Alberto Pascual-Montano &, 2013. "Sumoylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding to specific motifs," Nature Communications, Nature, vol. 4(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3980
    DOI: 10.1038/ncomms3980
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    1. Xueqing Wang & Quanlong Jiang & Hongdao Zhang & Zhidong He & Yuanyuan Song & Yifan Chen & Na Tang & Yifei Zhou & Yiping Li & Adam Antebi & Ligang Wu & Jing-Dong J. Han & Yidong Shen, 2024. "Tissue-specific profiling of age-dependent miRNAomic changes in Caenorhabditis elegans," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Bin Yu & Hekai Li & Zhaowenbin Zhang & Peier Chen & Ling Wang & Xianglin Fan & Xiaodong Ning & Yuxuan Pan & Feiran Zhou & Xinyi Hu & Jiang Chang & Caiwen Ou, 2023. "Extracellular vesicles engineering by silicates-activated endothelial progenitor cells for myocardial infarction treatment in male mice," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    3. Oskar Staufer & Gösta Gantner & Ilia Platzman & Klaus Tanner & Imre Berger & Joachim P. Spatz, 2022. "Bottom-up assembly of viral replication cycles," Nature Communications, Nature, vol. 13(1), pages 1-10, December.

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