Oral Presentation Australasian Extracellular Vesicles Conference 2018

RNA motif-guided exosomal microRNA export regulated by lipid raft protein Caveolin-1 (#13)

Harley R Robinson 1 2 , Jayde E Ruelcke 2 , Amanda Lewis 3 , Charles S Bond 3 , Archa H Fox 3 , Vandhana Bharti 4 , Shivangi Wani 4 , Nicole Cloonan 1 , Rob Parton 4 , Alexandre Cristino 2 , Michelle M Hill 1 2
  1. QIMRBerghofer, Herston, QLD, Australia
  2. UQ Diamantina Institute , Brisbane, QLD, Australia
  3. The Univeristy of Western Australia, Perth, WA, Australia
  4. Institute for Molecular Bioscience, UQ, Brisbane, QLD, Australia

 Extracellular vesicles, including exosomes and microvesicles, mediate intercellular communication by delivering molecular information to target cells. However, it is not clear how specific molecules are selected for export. Due to the enriched cholesterol and sphingolipid content of extracellular vesicles, we focus on the role of lipid raft proteins caveolin-1 and cavin-1 on vesicular miRNA export in a prostate cancer cell line, PC3. Here we reveal a novel mechanism by which caveolin-1 modulates the localization of heterogeneous nuclear ribonucleoprotein K (hnRNPK) to control the repertoire of miRNA selectively loaded to exosomes. This included miRNAs, such as miR-148a-3p and the miR-200 family, known to participate in pro-oncogenic activity. We demonstrate direct binding of hnRNPK to an export motif, AsUG, and in situ co-localization by microscopy, thus indicating sequence specificity of loaded exosomal miRNAs. These results provide a hereto missing link between lipid raft proteome and selective exosome cargo export.