TY - JOUR
T1 - hnRNPA2B1 inhibits the exosomal export of miR-503 in endothelial cells
AU - Pérez-Boza, Jennifer
AU - Boeckx, Amandine
AU - Lion, Michele
AU - Dequiedt, Franck
AU - Struman, Ingrid
PY - 2020/11/1
Y1 - 2020/11/1
N2 - 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.
AB - 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.
KW - EVs
KW - Exosomal export
KW - Exosomes
KW - MicroRNAs
KW - RNA-binding proteins
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85077217403&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/31894362
U2 - 10.1007/s00018-019-03425-6
DO - 10.1007/s00018-019-03425-6
M3 - Article
C2 - 31894362
VL - 77
SP - 4413
EP - 4428
JO - Cellular and Molecular Life Sciences
JF - Cellular and Molecular Life Sciences
SN - 1420-682X
IS - 21
ER -