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ミシマ ユウイチロウ
Mishima Yuichiro
三嶋 雄一郎 所属 京都産業大学 生命科学部 先端生命科学科 職種 教授 |
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| 言語種別 | 英語 |
| 発行・発表の年月 | 2023/11 |
| 形態種別 | 研究論文 |
| 査読 | 査読あり |
| 標題 | Glycosylated queuosines in tRNAs optimize translational rate and post-embryonic growth. |
| 執筆形態 | その他 |
| 掲載誌名 | Cell |
| 掲載区分 | 国外 |
| 著者・共著者 | Xuewei Zhao,Ding Ma,Kensuke Ishiguro,Hironori Saito,Shinichiro Akichika,Ikuya Matsuzawa,Mari Mito,Toru Irie,Kota Ishibashi,Kimi Wakabayashi,Yuriko Sakaguchi,Takeshi Yokoyama,Yuichiro Mishima,Mikako Shirouzu,Shintaro Iwasaki,Takeo Suzuki,Tsutomu Suzuki |
| 概要 | Transfer RNA (tRNA) modifications are critical for protein synthesis. Queuosine (Q), a 7-deaza-guanosine derivative, is present in tRNA anticodons. In vertebrate tRNAs for Tyr and Asp, Q is further glycosylated with galactose and mannose to generate galQ and manQ, respectively. However, biogenesis and physiological relevance of Q-glycosylation remain poorly understood. Here, we biochemically identified two RNA glycosylases, QTGAL and QTMAN, and successfully reconstituted Q-glycosylation of tRNAs using nucleotide diphosphate sugars. Ribosome profiling of knockout cells revealed that Q-glycosylation slowed down elongation at cognate codons, UAC and GAC (GAU), respectively. We also found that galactosylation of Q suppresses stop codon readthrough. Moreover, protein aggregates increased in cells lacking Q-glycosylation, indicating that Q-glycosylation contributes to proteostasis. Cryo-EM of human ribosome-tRNA complex revealed the molecular basis of codon recognition regulated by Q-glycosylations. Furthermore, zebrafish qtgal and qtman knockout lines displayed shortened body length, implying that Q-glycosylation is required for post-embryonic growth in vertebrates. |
| DOI | 10.1016/j.cell.2023.10.026 |
| PMID | 37992713 |