Maru Yoshiro    Department   School of Medicine, School of Medicine    Position   Professor and Division head
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