Queuosine modification protects cognate tRNAs against ribonuclease cleavage

Eukaryotic transfer RNAs (tRNA) contain on average 13 modifications that perform a wide range of roles in translation and in the generation of tRNA fragments that regulate gene expression. Queuosine (Q) modification occurs in the wobble anticodon position of tRNAs for amino acids His, Asn, Tyr, and...

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Bibliographic Details
Published in:RNA (Cambridge) 2018-10, Vol.24 (10), p.1305-1313
Main Authors: Wang, Xiaoyun, Matuszek, Zaneta, Huang, Yong, Parisien, Marc, Dai, Qing, Clark, Wesley, Schwartz, Michael H, Pan, Tao
Format: Article
Language:English
Subjects:
Angiogenin
Cell lines
Eukaryotes
Gene expression
Intestinal microflora
Microbiomes
Queuosine
Ribonuclease
Ribonucleic acid
RNA
RNA modification
tRNA
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Summary:Eukaryotic transfer RNAs (tRNA) contain on average 13 modifications that perform a wide range of roles in translation and in the generation of tRNA fragments that regulate gene expression. Queuosine (Q) modification occurs in the wobble anticodon position of tRNAs for amino acids His, Asn, Tyr, and Asp. In eukaryotes, Q modification is fully dependent on diet or on gut microbiome in multicellular organisms. Despite decades of study, cellular roles of Q modification remain to be fully elucidated. Here we show that in human cells, Q modification specifically protects its cognate tRNA and tRNA against cleavage by ribonucleases. We generated cell lines that contain completely depleted or fully Q-modified tRNAs. Using these resources, we found that Q modification significantly reduces angiogenin cleavage of its cognate tRNAs in vitro. Q modification does not change the cellular abundance of the cognate full-length tRNAs, but alters the cellular content of their fragments in vivo in the absence and presence of stress. Our results provide a new biological aspect of Q modification and a mechanism of how Q modification alters small RNA pools in human cells.
ISSN:1355-8382
1469-9001
DOI:10.1261/rna.067033.118