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CD47 interactions with exportin-1 limit the targeting of m7G-modified RNAs to extracellular vesicles

Sukhbir Kaur1, Alejandra Cavazos Saldana1, Abdel G Elkahloun2

  • 1Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 10 Room 2S235, 10 Center Dr, Bethesda, MD, 20892-1500, USA.

Journal of Cell Communication and Signaling
|November 29, 2021
PubMed

Insights

CD47 signaling restricts the release of specific RNA molecules into extracellular vesicles (EVs). This occurs through CD47

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Extracellular Vesicle Biology

Background:

  • CD47, a self-marker and receptor, is present in extracellular vesicles (EVs).
  • T cell EVs carrying CD47 influence target cells via RNA delivery.
  • Specific RNAs are enriched in CD47-positive EVs.

Purpose of the Study:

  • To elucidate the mechanisms by which CD47 regulates RNA trafficking into EVs.
  • To investigate the interaction of CD47 with the nuclear export machinery.

Main Methods:

  • Mass spectrometry to identify CD47-interacting proteins.
  • Coimmunoprecipitation to confirm protein interactions.
  • Leptomycin B treatment to inhibit exportin-1.
  • Transcriptomic analysis of EVs from wild-type and CD47-deficient cells.

Main Results:

  • CD47 interacts with ubiquilin-1 and the exportin-1/Ran nuclear export complex.
  • Inhibition of exportin-1 by leptomycin B increased m7G-modified RNA levels in EVs.
  • CD47 deficiency led to global enrichment of m7G-modified microRNAs and mRNAs in EVs.
  • Decreased CD47 expression or thrombospondin-1 treatment enhanced EV RNA levels.

Conclusions:

  • CD47 signaling limits the trafficking of m7G-modified RNAs to EVs.
  • CD47 interacts with the exportin-1/Ran complex to control RNA export.
  • This interaction regulates the release of specific RNAs via EVs.
Keywords:
CD47Exportin-1Extracellular vesiclesMicro-RNARNA traffickingUbiquilin-1

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