Details

Autor(en) / Beteiligte

• Zhao, Xuewei
• Ma, Ding
• Ishiguro, Kensuke
• Saito, Hironori
• Akichika, Shinichiro
• Matsuzawa, Ikuya
• Mito, Mari
• Irie, Toru
• Ishibashi, Kota
• Wakabayashi, Kimi
• Sakaguchi, Yuriko
• Yokoyama, Takeshi
• Mishima, Yuichiro
• Shirouzu, Mikako
• Iwasaki, Shintaro
• Suzuki, Takeo
• Suzuki, Tsutomu

Titel

Glycosylated queuosines in tRNAs optimize translational rate and post-embryonic growth

Ist Teil von

• Cell, 2023-12, Vol.186 (25), p.5517-5535.e24

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2023

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

• 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. [Display omitted] •Two tRNA Q-glycosylation enzymes QTGAL and QTMAN were identified•Q-glycosylation of tRNA contributes to optimal translation and proteostasis•Structural analyses revealed molecular basis of codon recognition by Q-glycosylation•Q-glycosylation of tRNA is required for post-embryonic growth of zebrafish Queosine (Q) is a modified nucleoside present in tRNA anticodons. Identification and characterization of two vertebrate Q-glycosylases unveil new regulatory mechanism in protein translation and proteostasis.