The importance of ago 1 and 4 in post-transcriptional gene regulatory function of TRF5-gluctc, an respiratory syncytial virus-induced tRNA-derived RNA fragment

Eun Jin Choi, Junping Ren, Ke Zhang, Wenzhe Wu, Yong Sun Lee, Inhan Lee, Xiaoyong Bao

Research output: Contribution to journalArticlepeer-review

Abstract

Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in infants, the elderly, and immune-compromised patients. It is also a significant contributor to upper respiratory tract infection in the pediatric population. However, its disease mechanisms are still largely unknown. We have recently shown that a tRNA-derived RNA fragment (tRF) from the 5-end of mature tRNA encoding GluCTC (tRF5-GluCTC), a recently discovered non-coding RNA, is functionally important for RSV replication and host gene regulation at the post-transcriptional level. However, how tRF5-GluCTC carries out the gene regulation is not fully known. In this study, we found that tRF5-GluCTC has impaired gene trans-silencing function in cells deficient of AGO1 or 4, while AGO2 and 3 seem not involved in tRF5-GluCTC-mediated gene regulation. By pulling down individual AGO protein, we discovered that tRF5-GluCTC is detectable only in the AGO4 complex, confirming the essential role of AGO4 in gene regulation and also suggesting that AGO1 contributes to the gene trans-silencing activity of tRF5-GluCTC in an atypical way. We also found that the P protein of RSV is associated with both AGO1 and 4 and AGO4 deficiency leads to reduced infectious viral particles. In summary, this study demonstrates the importance of AGO1 and 4 in mediating the gene trans-silencing function of tRF5-GluCTC.

Original languageEnglish (US)
Article number8766
Pages (from-to)1-11
Number of pages11
JournalInternational journal of molecular sciences
Volume21
Issue number22
DOIs
StatePublished - Nov 2 2020

Keywords

  • Argonaute
  • Post-transcriptional gene regulation
  • RSV
  • TRNA-derived RNA fragments

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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