マル　ヨシロウ   Maru Yoshiro   丸　義朗    所属   医学部 医学科    職種   教授・基幹分野長
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Extracellular mRNA transported to the nucleus exerts translation-independent function.
掲載誌名	正式名：Nature communications 略　 称：Nat Commun ISSNコード：20411723/20411723
掲載区分	国外
巻・号・頁	12(1),pp.3655
著者・共著者	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
担当区分	最終著者
発行年月	2021/06
概要	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