| Literature DB >> 34135341 |
Takeshi Tomita1,2, Masayoshi Kato1,2, Taishi Mishima3, Yuta Matsunaga3, Hideki Sanjo4, Ken-Ichi Ito5, Kentaro Minagawa6, Toshimitsu Matsui7, Hiroyuki Oikawa8, Satoshi Takahashi8, Toshifumi Takao9, Noriki Iwai10, Takashi Mino10, Osamu Takeuchi10, Yoshiro Maru11, Sachie Hiratsuka12,13.
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.Entities:
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Year: 2021 PMID： 34135341 DOI： 10.1038/s41467-021-23969-1
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919