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タイトル: | Translational recoding by chemical modification of non-AUG start codon ribonucleotide bases |
著者: | Fujita, Yoshihiko https://orcid.org/0000-0001-6321-2121 (unconfirmed) Kameda, Takeru Singh, Chingakham Ranjit Pepper, Whitney Cecil, Ariana Hilgers, Madelyn Thornton, Mackenzie Asano, Izumi Moravek, Carter Togashi, Yuichi Saito, Hirohide Asano, Katsura |
著者名の別形: | 藤田, 祥彦 亀田, 健 冨樫, 祐一 齊藤, 博英 浅野, 桂 |
発行日: | Apr-2022 |
出版者: | American Association for the Advancement of Science (AAAS) |
誌名: | Science Advances |
巻: | 8 |
号: | 14 |
論文番号: | eabm8501 |
抄録: | In contrast to prokaryotes wherein GUG and UUG are permissive start codons, initiation frequencies from non-AUG codons are generally low in eukaryotes, with CUG being considered as strongest. Here, we report that combined 5-cytosine methylation (5mC) and pseudouridylation (Ψ) of near-cognate non-AUG start codons convert GUG and UUG initiation strongly favored over CUG initiation in eukaryotic translation under a certain context. This prokaryotic-like preference is attributed to enhanced NUG initiation by Ψ in the second base and reduced CUG initiation by 5mC in the first base. Molecular dynamics simulation analysis of tRNAiMet anticodon base pairing to the modified codons demonstrates that Ψ universally raises the affinity of codon:anticodon pairing within the ribosomal preinitiation complex through partially mitigating discrimination against non-AUG codons imposed by eukaryotic initiation factor 1. We propose that translational control by chemical modifications of start codon bases can offer a new layer of proteome diversity regulation and therapeutic mRNA technology. |
記述: | 遺伝暗号開始コドンの修飾がmRNAの性能を変える --修飾塩基によりmRNAからタンパク質の作られやすさが変わる新しいメカニズムを発見!--. 京都大学プレスリリース. 2022-04-11. |
著作権等: | Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). This is an open-access article distributed under the terms of the Creative Commons Attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
URI: | http://hdl.handle.net/2433/269451 |
DOI(出版社版): | 10.1126/sciadv.abm8501 |
PubMed ID: | 35394828 |
関連リンク: | https://www.cira.kyoto-u.ac.jp/j/pressrelease/news/220411-100000.html |
出現コレクション: | 学術雑誌掲載論文等 |
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