Author:
Wang Xiaoyun,Matuszek Zaneta,Huang Yong,Parisien Marc,Dai Qing,Clark Wesley,Schwartz Michael H.,Pan Tao
Abstract
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 tRNAHis and tRNAAsn 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.
Funder
Department of Defense
Congressionally Directed Medical Research Programs
National Institutes of Health
National Institute of Diabetes and Digestive and Kidney Diseases
Publisher
Cold Spring Harbor Laboratory
Cited by
92 articles.
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