Distinct mechanisms of microrna sorting into cancer cell-derived extracellular vesicle subtypes

Morayma M. Temoche-Diaz, Matthew J. Shurtleff, Ryan M. Nottingham, Jun Yao, Raj P. Fadadu, Alan M. Lambowitz, Randy Schekman

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Extracellular vesicles (EVs) encompass a variety of vesicles secreted into the extracellular space. EVs have been implicated in promoting tumor metastasis, but the molecular composition of tumor-derived EV sub-types and the mechanisms by which molecules are sorted into EVs remain mostly unknown. We report the separation of two small EV sub-populations from a metastatic breast cancer cell line, with biochemical features consistent with different sub-cellular origins. These EV sub-types use different mechanisms of miRNA sorting (selective and non- selective), suggesting that sorting occurs via fundamentally distinct processes, possibly dependent on EV origin. Using biochemical and genetic tools, we identified the Lupus La protein as mediating sorting of selectively packaged miRNAs. We found that two motifs embedded in miR-122 are responsible for high-affinity binding to Lupus La and sorting into vesicles formed in a cell-free reaction. Thus, tumor cells can simultaneously deploy multiple EV species using distinct sorting mechanisms that may enable diverse functions in normal and cancer biology.

Original languageEnglish (US)
Article numbere47544
JournaleLife
Volume8
DOIs
StatePublished - Aug 2019

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MicroRNAs
Sorting
Cells
Tumors
Neoplasms
Extracellular Vesicles
Extracellular Space
Molecules
Molecular Biology
Chemical analysis
Breast Neoplasms
Neoplasm Metastasis
Proteins
Cell Line
Population

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Temoche-Diaz, M. M., Shurtleff, M. J., Nottingham, R. M., Yao, J., Fadadu, R. P., Lambowitz, A. M., & Schekman, R. (2019). Distinct mechanisms of microrna sorting into cancer cell-derived extracellular vesicle subtypes. eLife, 8, [e47544]. https://doi.org/10.7554/eLife.47544

Distinct mechanisms of microrna sorting into cancer cell-derived extracellular vesicle subtypes. / Temoche-Diaz, Morayma M.; Shurtleff, Matthew J.; Nottingham, Ryan M.; Yao, Jun; Fadadu, Raj P.; Lambowitz, Alan M.; Schekman, Randy.

In: eLife, Vol. 8, e47544, 08.2019.

Research output: Contribution to journalArticle

Temoche-Diaz, MM, Shurtleff, MJ, Nottingham, RM, Yao, J, Fadadu, RP, Lambowitz, AM & Schekman, R 2019, 'Distinct mechanisms of microrna sorting into cancer cell-derived extracellular vesicle subtypes', eLife, vol. 8, e47544. https://doi.org/10.7554/eLife.47544
Temoche-Diaz, Morayma M. ; Shurtleff, Matthew J. ; Nottingham, Ryan M. ; Yao, Jun ; Fadadu, Raj P. ; Lambowitz, Alan M. ; Schekman, Randy. / Distinct mechanisms of microrna sorting into cancer cell-derived extracellular vesicle subtypes. In: eLife. 2019 ; Vol. 8.
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