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Extracellular mRNA transported to the nucleus exerts translation-independent function

Author

Listed:
  • Takeshi Tomita

    (Shinshu University, School of Medicine
    Shinshu University, School of Medicine)

  • Masayoshi Kato

    (Shinshu University, School of Medicine
    Shinshu University, School of Medicine)

  • Taishi Mishima

    (Tokyo Women’s Medical University)

  • Yuta Matsunaga

    (Tokyo Women’s Medical University)

  • Hideki Sanjo

    (Shinshu University, School of Medicine)

  • Ken-ichi Ito

    (Shinshu University, School of Medicine)

  • Kentaro Minagawa

    (Penn State College of Medicine)

  • Toshimitsu Matsui

    (Nishiwaki Municipal Hospital)

  • Hiroyuki Oikawa

    (Tohoku University)

  • Satoshi Takahashi

    (Tohoku University)

  • Toshifumi Takao

    (Osaka University)

  • Noriki Iwai

    (Kyoto University)

  • Takashi Mino

    (Kyoto University)

  • Osamu Takeuchi

    (Kyoto University)

  • Yoshiro Maru

    (Tokyo Women’s Medical University)

  • Sachie Hiratsuka

    (Shinshu University, School of Medicine
    Shinshu University, School of Medicine)

Abstract

RNA in extracellular vesicles (EVs) are uptaken by cells, where they regulate fundamental cellular functions. EV-derived mRNA in recipient cells can be translated. However, it is still elusive whether “naked nonvesicular extracellular mRNA” (nex-mRNA) that are not packed in EVs can be uptaken by cells and, if so, whether they have any functions in recipient cells. Here, we show the entrance of nex-mRNA in the nucleus, where they exert a translation-independent function. Human nex-interleukin-1β (IL1β)-mRNA outside cells proved to be captured by RNA-binding zinc finger CCCH domain containing protein 12D (ZC3H12D)-expressing human natural killer (NK) cells. ZC3H12D recruited to the cell membrane binds to the 3′-untranslated region of nex-IL1β-mRNA and transports it to the nucleus. The nex-IL1β-mRNA in the NK cell nucleus upregulates antiapoptotic gene expression, migration activity, and interferon-γ production, leading to the killing of cancer cells and antimetastasis in mice. These results implicate the diverse actions of mRNA.

Suggested Citation

  • Takeshi Tomita & Masayoshi Kato & Taishi Mishima & Yuta Matsunaga & Hideki Sanjo & Ken-ichi Ito & Kentaro Minagawa & Toshimitsu Matsui & Hiroyuki Oikawa & Satoshi Takahashi & Toshifumi Takao & Noriki , 2021. "Extracellular mRNA transported to the nucleus exerts translation-independent function," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23969-1
    DOI: 10.1038/s41467-021-23969-1
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