Queuosine modification protects cognate tRNAs against ribonuclease cleavage
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jul 03, 2018
- Source ID
- 10.1261/rna.067033.118
Entities
People
- Marc Parisien
- Michael H. Schwartz
- Qing Dai
- Tao Pan
- Wesley Clark
- Xiaoyun Wang
- Yong Huang
- Zaneta Matuszek
Organizations
- Congressionally Directed Medical Research Programs
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Institutes of Health
- United States Department of Defense