PUBLICATION
Glycosylated queuosines in tRNAs optimize translational rate and post-embryonic growth
- Authors
- 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.
- ID
- ZDB-PUB-231123-7
- Date
- 2023
- Source
- Cell 186(25): 5517-5535.e24 (Journal)
- Registered Authors
- Mishima, Yuichiro
- Keywords
- RNA modification, galQ, galactosylqueuosine, manQ, mannosyl-queuosine, proteostasis, queuosine, ribosome, tRNA, translation
- MeSH Terms
-
- Animals
- Anticodon
- Cell Line
- Codon
- Glycosylation
- Humans
- Nucleic Acid Conformation
- Nucleoside Q/chemistry
- Nucleoside Q/genetics
- Nucleoside Q/metabolism
- RNA, Transfer*/chemistry
- RNA, Transfer*/metabolism
- Rats
- Swine
- Zebrafish/metabolism
- PubMed
- 37992713 Full text @ Cell
Citation
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. (2023) Glycosylated queuosines in tRNAs optimize translational rate and post-embryonic growth. Cell. 186(25):5517-5535.e24.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping