Distinct mechanisms of microRNA sorting into cancer cell-derived extracellular vesicle subtypes
| Autor: | Randy Schekman, Ryan M. Nottingham, Matthew J Shurtleff, Jun Yao, Raj P. Fadadu, Alan M. Lambowitz, Morayma M. Temoche-Diaz |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Autoantigens Metastasis 0302 clinical medicine 2.1 Biological and endogenous factors Biology (General) Aetiology Lupus La Cancer Cancer Biology cancer biology 0303 health sciences Tumor Chemistry General Neuroscience Vesicle Sorting RNA-Binding Proteins General Medicine Extracellular vesicle Cell biology Ribonucleoproteins 030220 oncology & carcinogenesis Medicine Biotechnology Research Article Human Protein Binding QH301-705.5 Science 1.1 Normal biological development and functioning Chemical biology Breast Neoplasms chemical biology General Biochemistry Genetics and Molecular Biology Cell Line 03 medical and health sciences Extracellular Vesicles Underpinning research Biochemistry and Chemical Biology Cell Line Tumor Breast Cancer microRNA medicine Extracellular Humans biochemistry human 030304 developmental biology miRNA General Immunology and Microbiology Biological Transport medicine.disease multivesicular bodies MicroRNAs 030104 developmental biology Cell culture Cancer cell Biochemistry and Cell Biology |
| Zdroj: | eLife eLife, Vol 8 (2019) |
| Popis: | 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 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 some 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. |
| Databáze: | OpenAIRE |
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