Queuosine modification protects cognate tRNAs against ribonuclease cleavage
- Xiaoyun Wang1,
- Zaneta Matuszek1,
- Yong Huang2,
- Marc Parisien3,
- Qing Dai1,
- Wesley Clark1,
- Michael H. Schwartz1 and
- Tao Pan1
- 1Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois 60637, USA
- 2Department of Medicine, Knapp Center for Biomedical Discovery, University of Chicago, Chicago, Illinois 60637, USA
- 3Alan Edwards Centre for Research on Pain, McGill University, Montréal, QC H3A 0G4, Canada
- Corresponding authors: xwang13{at}uchicago.edu, taopan{at}uchicago.edu
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.
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Article is online at http://www.rnajournal.org/cgi/doi/10.1261/rna.067033.118.
- Received April 27, 2018.
- Accepted June 26, 2018.
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