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タイトル: | Translation-dependent unwinding of stem–loops by UPF1 licenses Regnase-1 to degrade inflammatory mRNAs |
著者: | Mino, Takashi https://orcid.org/0000-0002-9562-008X (unconfirmed) Iwai, Noriki Endo, Masayuki Inoue, Kentaro Akaki, Kotaro Hia, Fabian Uehata, Takuya Emura, Tomoko Hidaka, Kumi Suzuki, Yutaka Standley, Daron M Okada-Hatakeyama, Mariko Ohno, Shigeo Sugiyama, Hiroshi https://orcid.org/0000-0001-8923-5946 (unconfirmed) Yamashita, Akio Takeuchi, Osamu https://orcid.org/0000-0002-1260-6232 (unconfirmed) |
著者名の別形: | 三野, 享史 岩井, 紀貴 遠藤, 政幸 井上, 健太郎 赤木, 宏太朗 ヒヤ, フェビエン 植畑, 拓也 江村, 智子 日高, 久美 鈴木, 穣 岡田, 眞里子 大野, 茂男 杉山, 弘 山下, 暁朗 竹内, 理 |
発行日: | 19-Sep-2019 |
出版者: | Oxford University Press (OUP) |
誌名: | Nucleic Acids Research |
巻: | 47 |
号: | 16 |
開始ページ: | 8838 |
終了ページ: | 8859 |
抄録: | Regnase-1-mediated mRNA decay (RMD), in which inflammatory mRNAs harboring specific stem–loop structures are degraded, is a critical part of proper immune homeostasis. Prior to initial translation, Regnase-1 associates with target stem–loops but does not carry out endoribonucleolytic cleavage. Single molecule imaging revealed that UPF1 is required to first unwind the stem–loops, thus licensing Regnase-1 to proceed with RNA degradation. Following translation, Regnase-1 physically associates with UPF1 using two distinct points of interaction: The Regnase-1 RNase domain binds to SMG1-phosphorylated residue T28 in UPF1; in addition, an intrinsically disordered segment in Regnase-1 binds to the UPF1 RecA domain, enhancing the helicase activity of UPF1. The SMG1-UPF1–Regnase-1 axis targets pioneer rounds of translation and is critical for rapid resolution of inflammation through restriction of the number of proteins translated by a given mRNA. Furthermore, small-molecule inhibition of SMG1 prevents RNA unwinding in dendritic cells, allowing post-transcriptional control of innate immune responses. |
記述: | 炎症が制御される新たなRNA分解メカニズムを解明 --新たな免疫賦活化法の開発に道筋--. 京都大学プレスリリース. 2019-07-25. |
著作権等: | © The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
URI: | http://hdl.handle.net/2433/243190 |
DOI(出版社版): | 10.1093/nar/gkz628 |
PubMed ID: | 31329944 |
関連リンク: | https://www.kyoto-u.ac.jp/ja/research-news/2019-07-25 |
出現コレクション: | 学術雑誌掲載論文等 |
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