Selective cleavage of ncRNA and antiviral activity by RNase2/EDN in THP1-induced macrophages

Lu Lu*, Jiarui Li, Ranlei Wei, Irene Guidi, Luca Cozzuto, Julia Ponomarenko, Guillem Prats-Ejarque, Ester Boix

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

5 Citations (Scopus)


RNase2 is the member of the RNaseA family most abundant in macrophages. Here, we knocked out RNase2 in THP-1 cells and analysed the response to Respiratory Syncytial Virus (RSV). RSV induced RNase2 expression, which significantly enhanced cell survival. Next, by cP-RNAseq sequencing, which amplifies the cyclic-phosphate endonuclease products, we analysed the ncRNA population. Among the ncRNAs accumulated in WT vs KO cells, we found mostly tRNA-derived fragments (tRFs) and second miRNAs. Differential sequence coverage identified tRFs from only few parental tRNAs, revealing a predominant cleavage at anticodon and D-loops at U/C (B1) and A (B2) sites. Selective tRNA cleavage was confirmed in vitro using the recombinant protein. Likewise, only few miRNAs were significantly more abundant in WT vs RNase2-KO cells. Complementarily, by screening of a tRF & tiRNA array, we identified an enriched population associated to RNase2 expression and RSV exposure. The results confirm the protein antiviral action and provide the first evidence of its cleavage selectivity on ncRNAs.

Original languageEnglish
Article number209
Number of pages18
JournalCellular and Molecular Life Sciences
Issue number4
Early online date26 Mar 2021
Publication statusPublished - Apr 2022


  • RNase
  • RSV
  • Virus
  • miRNA
  • tRF
  • tRNA


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