| RRC ID |
65692
|
| 著者 |
Tomita T, Kato M, Mishima T, Matsunaga Y, Sanjo H, Ito KI, Minagawa K, Matsui T, Oikawa H, Takahashi S, Takao T, Iwai N, Mino T, Takeuchi O, Maru Y, Hiratsuka S.
|
| タイトル |
Extracellular mRNA transported to the nucleus exerts translation-independent function.
|
| ジャーナル |
Nat Commun
|
| 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.
|
| 巻・号 |
12(1)
|
| ページ |
3655
|
| 公開日 |
2021-6-16
|
| DOI |
10.1038/s41467-021-23969-1
|
| PII |
10.1038/s41467-021-23969-1
|
| PMID |
34135341
|
| PMC |
PMC8208975
|
| MeSH |
3' Untranslated Regions
Animals
Antineoplastic Agents / pharmacology
Cell Cycle Proteins / metabolism
Cell Line, Tumor
Cell Membrane / metabolism
Cell Nucleus / metabolism*
Culture Media, Conditioned / metabolism
Endoribonucleases / metabolism
Extracellular Space / metabolism*
Humans
Interleukin-1beta / genetics
Interleukin-1beta / metabolism
Killer Cells, Natural / metabolism
Mice
Protein Binding
RNA, Messenger / genetics
RNA, Messenger / metabolism*
RNA, Messenger / pharmacology
RNA-Binding Proteins / metabolism
|
| IF |
12.121
|
| リソース情報 |
| ヒト・動物細胞 |
LLC(RCB0558)
RAW 264(RCB0535)
THP-1(RCB1189)
293T(RCB2202)
B16 melanoma(RCB1283) |
