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Extracellular mRNA transported to the nucleus exerts translation-independent function

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 cel...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208975/
https://www.ncbi.nlm.nih.gov/pubmed/34135341
http://dx.doi.org/10.1038/s41467-021-23969-1
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author 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
author_facet 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
author_sort Tomita, Takeshi
collection PubMed
description 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.
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spelling pubmed-82089752021-07-01 Extracellular mRNA transported to the nucleus exerts translation-independent function 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 Nat Commun Article 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. Nature Publishing Group UK 2021-06-16 /pmc/articles/PMC8208975/ /pubmed/34135341 http://dx.doi.org/10.1038/s41467-021-23969-1 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
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
Extracellular mRNA transported to the nucleus exerts translation-independent function
title Extracellular mRNA transported to the nucleus exerts translation-independent function
title_full Extracellular mRNA transported to the nucleus exerts translation-independent function
title_fullStr Extracellular mRNA transported to the nucleus exerts translation-independent function
title_full_unstemmed Extracellular mRNA transported to the nucleus exerts translation-independent function
title_short Extracellular mRNA transported to the nucleus exerts translation-independent function
title_sort extracellular mrna transported to the nucleus exerts translation-independent function
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208975/
https://www.ncbi.nlm.nih.gov/pubmed/34135341
http://dx.doi.org/10.1038/s41467-021-23969-1
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