Journal
GENOME BIOLOGY
Volume 21, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s13059-020-02145-6
Keywords
Cell surface; Extracellular RNA; Cell membrane; Single cell; Cell-environment interaction; Monocyte; Endothelial cells
Funding
- National Institutes of Health [DP1HD087990, R01HL145170]
- National Science Foundation [DMR-1904702]
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Background Compared to proteins, glycans, and lipids, much less is known about RNAs on the cell surface. We develop a series of technologies to test for any nuclear-encoded RNAs that are stably attached to the cell surface and exposed to the extracellular space, hereafter called membrane-associated extracellular RNAs (maxRNAs). Results We develop a technique called Surface-seq to selectively sequence maxRNAs and validate two Surface-seq identified maxRNAs by RNA fluorescence in situ hybridization. To test for cell-type specificity of maxRNA, we use antisense oligos to hybridize to single-stranded transcripts exposed on the surface of human peripheral blood mononuclear cells (PBMCs). Combining this strategy with imaging flow cytometry, single-cell RNA sequencing, and maxRNA sequencing, we identify monocytes as the major type of maxRNA+ PBMCs and prioritize 11 candidate maxRNAs for functional tests. Extracellular application of antisense oligos ofFNDC3BandCTSStranscripts inhibits monocyte adhesion to vascular endothelial cells. Conclusions Collectively, these data highlight maxRNAs as functional components of the cell surface, suggesting an expanded role for RNA in cell-cell and cell-environment interactions.
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