| RRC ID |
77411
|
| 著者 |
Zhao X, Ma D, Ishiguro K, Saito H, Akichika S, Matsuzawa I, Mito M, Irie T, Ishibashi K, Wakabayashi K, Sakaguchi Y, Yokoyama T, Mishima Y, Shirouzu M, Iwasaki S, Suzuki T, Suzuki T.
|
| タイトル |
Glycosylated queuosines in tRNAs optimize translational rate and post-embryonic growth.
|
| ジャーナル |
Cell
|
| Abstract |
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.
|
| 公開日 |
2023-11-17
|
| DOI |
10.1016/j.cell.2023.10.026
|
| PII |
S0092-8674(23)01177-7
|
| PMID |
37992713
|
| IF |
38.637
|
| リソース情報 |
| ヒト・動物細胞 |
HeLa(RCB0007)
293(RCB1637) |
