Journal
CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 77, Issue 21, Pages 4413-4428Publisher
SPRINGER BASEL AG
DOI: 10.1007/s00018-019-03425-6
Keywords
Exosomes; EVs; MicroRNAs; Exosomal export; RNA-binding proteins
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Funding
- University of Liege (ULiege)
- Fonds National de la Recherche Scientifique (FNRS)
- Televie
- Fonds Leon Fredericq
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The chemotherapeutic drug epirubicin increases the exosomal export of miR-503 in endothelial cells. To understand the mechanisms behind this process, we transfected endothelial cells with miR-503 carrying a biotin tag. Then, we pulled-down the proteins interacting with miR-503 and studied their role in microRNA exosomal export. A total of four different binding partners were identified by mass spectrometry and validated by western blotting and negative controls, among them ANXA2 and hnRNPA2B1. Using knock-down systems combined with pull-down analysis, we determined that epirubicin mediates the export of miR-503 by disrupting the interaction between hnRNPA2B1 and miR-503. Then, both ANXA2 and miR-503 are sorted into exosomes while hnRNPA2B1 is relocated into the nucleus. The combination of these processes culminates in the increased export of miR-503. These results suggest, for the first time, that RNA-binding proteins can negatively regulate the exosomal sorting of microRNAs.
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