CD47 is a marker of self and a signaling receptor for thrombospondin-1 that is also a membrane
component of extracellular vesicles (EVs) released by various cell types. Previous studies identified CD47-dependent functional effects of EVs on target cells, mediated by delivery of their RNA contents, and enrichment of specific subsets of coding and noncoding RNAs in CD47+ EVs. Here, transcriptomic analyses of EVs released by human and murine cells revealed CD47-dependent enrichment of capped microRNAs and mRNAs. Knockdown or loss of CD47 in wild type Jurkat T cells or treatment with thrombospondin-1 enhanced levels of specific capped-RNAs released in EVs, and reexpressing CD47 in null cells decreased their levels. Mass spectrometry and co-immunoprecipitation identified specific interactions of CD47 with components of the exportin-1/Ran nuclear export complex and its known cargo proteins and between the CD47 cytoplasmic adapter ubiquilin-1 and the exportin-1/Ran complex. Interaction with CD47 was inhibited following alkylation of exportin-1 at Cys528 by leptomycin B. Leptomycin B treatment increased levels of cap-dependent RNAs and their association with exportin-1 in EVs released from wild type but not CD47-deficient cells. These results indicate that CD47
regulates the trafficking of cap-dependent RNAs to EVs through physical interactions with the exportin-1/Ran transport complex. Within the files, lmj1038 represents the control pulldown from CD47- JinB8 cells whereas lmj1039 is the CD47+ pulldown from wild-type Jurkat cells.
[doi:10.25345/C5NR5W]
[dataset license: CC0 1.0 Universal (CC0 1.0)]
Keywords: CD47 interactome ; extracellular vesicle
Principal Investigators: (in alphabetical order) |
Lisa Jenkins, NCI, NIH, United States |
Submitting User: | lisamiljenk |
Kaur S, Saldana AC, Elkahloun AG, Petersen JD, Arakelyan A, Singh SP, Jenkins LM, Kuo B, Reginauld B, Jordan DG, Tran AD, Wu W, Zimmerberg J, Margolis L, Roberts DD.
CD47 interactions with exportin-1 limit the targeting of m7G-modified RNAs to extracellular vesicles.
J Cell Commun Signal. 2022 Sep;16(3):397-419. Epub 2021 Nov 29.
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