Maru Yoshiro
Department School of Medicine, School of Medicine Position Professor and Division head |
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Article types | Original article |
Language | English |
Peer review | Peer reviewed |
Title | Extracellular mRNA transported to the nucleus exerts translation-independent function. |
Journal | Formal name:Nature communications Abbreviation:Nat Commun ISSN code:20411723/20411723 |
Domestic / Foregin | Foregin |
Volume, Issue, Page | 12(1),pp.3655 |
Author and coauthor | Tomita Takeshi, Kato Masayoshi, Mishima Taishi, Matsunaga Yuta, Sanjo Hideki, Ito Ken-Ichi, Minagawa Kentaro, Matsui Toshimitsu, Oikawa Hiroyuki, Takahashi Satoshi, Takao Toshifumi, Iwai Noriki, Mino Takashi, Takeuchi Osamu, Maru Yoshiro, Hiratsuka Sachie |
Authorship | Last author |
Publication date | 2021/06 |
Summary | 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. |
DOI | 10.1038/s41467-021-23969-1 |
PMID | 34135341 |