Identification and functional characterization of tRNA-derived RNA fragments (tRFs) in respiratory syncytial virus infection

Mol Ther. 2013 Feb;21(2):368-79. doi: 10.1038/mt.2012.237. Epub 2012 Nov 27.

Abstract

The discovery of small noncoding RNAs (sncRNAs) with regulatory functions is a recent breakthrough in biology. Among sncRNAs, microRNA (miRNA), derived from host or virus, has emerged as elements with high importance in control of viral replication and host responses. However, the expression pattern and functional aspects of other types of sncRNAs, following viral infection, are unexplored. In order to define expression patterns of sncRNAs, as well as to discover novel regulatory sncRNAs in response to viral infection, we applied deep sequencing to cells infected with human respiratory syncytial virus (RSV), the most common cause of bronchiolitis and pneumonia in babies. RSV infection leads to abundant production of transfer RNA (tRNA)-derived RNA Fragments (tRFs) that are ~30 nucleotides (nts) long and correspond to the 5'-half of mature tRNAs. At least one tRF, which is derived from tRNA-Glu-CTC, represses target mRNA in the cytoplasm and promotes RSV replication. This demonstrates that this tRF is not a random by-product of tRNA degradation but a functional molecule. The biogenesis of this tRF is also specific, as it is mediated by the endonuclease angiogenin (ANG), not by other nucleases. In summary, our study presents novel information on the induction of a functional tRF by viral infection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biosensing Techniques
  • Blotting, Northern
  • Bronchiolitis / genetics
  • Bronchiolitis / virology
  • Cell Differentiation
  • Cell Line, Tumor
  • Chromosome Mapping
  • Cytoplasm / metabolism
  • Epithelial Cells / cytology
  • Epithelial Cells / virology
  • Gene Expression Profiling
  • Gene Expression Regulation, Viral*
  • High-Throughput Nucleotide Sequencing / methods
  • Humans
  • Luciferases / genetics
  • Luciferases / metabolism
  • MicroRNAs / genetics
  • MicroRNAs / isolation & purification
  • Plasmids / genetics
  • Protein Biosynthesis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / isolation & purification*
  • RNA, Small Untranslated / genetics
  • RNA, Small Untranslated / isolation & purification
  • RNA, Transfer / genetics
  • RNA, Transfer / isolation & purification*
  • Real-Time Polymerase Chain Reaction
  • Respiratory Syncytial Virus Infections / genetics*
  • Respiratory Syncytial Virus Infections / metabolism
  • Respiratory Syncytial Virus, Human / genetics*
  • Respiratory Syncytial Virus, Human / physiology
  • Ribonuclease, Pancreatic / genetics
  • Ribonuclease, Pancreatic / metabolism
  • Virus Replication

Substances

  • MicroRNAs
  • RNA, Messenger
  • RNA, Small Interfering
  • RNA, Small Untranslated
  • RNA, Transfer
  • Luciferases
  • angiogenin
  • Ribonuclease, Pancreatic