RGD Reference Report - Glycosylated queuosines in tRNAs optimize translational rate and post-embryonic growth. - Rat Genome Database

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

Authors: 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 
Citation: Zhao X, etal., Cell. 2023 Dec 7;186(25):5517-5535.e24. doi: 10.1016/j.cell.2023.10.026. Epub 2023 Nov 21.
RGD ID: 401966881
Pubmed: PMID:37992713   (View Abstract at PubMed)
DOI: DOI:10.1016/j.cell.2023.10.026   (Journal Full-text)

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.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
B3gntl1RattRNA modification involved_inIDA PMID:37992713UniProt 
Gtdc1RattRNA modification involved_inIDA PMID:37992713UniProt 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Gtdc1RattRNA-queuosine(34) beta-mannosyltransferase activity enablesIDA PMID:37992713UniProt 
B3gntl1RattRNA-queuosine(34) galactosyltransferase activity enablesIDA PMID:37992713UniProt 

Objects Annotated

Genes (Rattus norvegicus)
B3gntl1  (UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase-like 1)
Gtdc1  (glycosyltransferase-like domain containing 1)


Additional Information