| First Author | Tomita T | Year | 2021 |
| Journal | Nat Commun | Volume | 12 |
| Issue | 1 | Pages | 3655 |
| PubMed ID | 34135341 | Mgi Jnum | J:347369 |
| Mgi Id | MGI:6725470 | Doi | 10.1038/s41467-021-23969-1 |
| Citation | Tomita T, et al. (2021) Extracellular mRNA transported to the nucleus exerts translation-independent function. Nat Commun 12(1):3655 |
| abstractText | 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-1beta (IL1beta)-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-IL1beta-mRNA and transports it to the nucleus. The nex-IL1beta-mRNA in the NK cell nucleus upregulates antiapoptotic gene expression, migration activity, and interferon-gamma production, leading to the killing of cancer cells and antimetastasis in mice. These results implicate the diverse actions of mRNA. |
