MEX3C interacts with adaptor-related protein complex 2 and involves in miR-451a exosomal sorting

PLoS One. 2017 Oct 5;12(10):e0185992. doi: 10.1371/journal.pone.0185992. eCollection 2017.


Some RNA species, especially microRNAs, are non-randomly sorted into exosomes, but how selectivity of RNA exosomal sorting is achieved is unknown. We found that all three variants of RNA-binding ubiquitin E3 ligase (MEX3C)-MEX3C-1, MEX3C-2, and MEX3C-3 -interact with adaptor-related protein complex 2 (AP-2), a cargo adaptor in clathrin-mediated endocytosis. MEX3C's C-terminal RING finger domain and the hnRNP K homology (KH) domain shared by the three MEX3C variants are both necessary for MEX3C/AP-2 interaction. MEX3C associates with the endolysosomal compartment through an endocytosis-like process. siRNA-mediated inhibition of the MEX3C or AP-2 complex substantially decreased exosomal but not cellular microRNA miR-451a expression. Exosomal sorting is ceramide-dependent but not ESCRT-dependent in microRNA miR-451a. That RNA-binding protein associates with membrane trafficking machinery, and that its involvement in exosomal microRNA expression, suggest the existence of a mechanism for specific recruiting of RNA molecules to endosomes for subsequent exosomal sorting.

MeSH terms

  • Adaptor Protein Complex 2 / metabolism*
  • Animals
  • Exosomes / metabolism*
  • HEK293 Cells
  • Humans
  • Mice
  • MicroRNAs / metabolism*
  • Protein Binding
  • RNA-Binding Proteins / metabolism*


  • Adaptor Protein Complex 2
  • MEX3c protein, mouse
  • MicroRNAs
  • Mirn451 microRNA, mouse
  • RNA-Binding Proteins