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

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...

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Detalles Bibliográficos
Autores: Lu, Lu|||0000-0002-0960-1529, Li, Jiarui|||0000-0001-5556-3001, Wei, RanLei|||0000-0002-0257-1603, Guidi, Irene, Cozzuto, Luca|||0000-0003-3194-8892, Ponomarenko, Julia|||0000-0002-1477-9444, Prats-Ejarque, Guillem|||0000-0002-8213-4947, Boix, Ester|||0000-0003-1790-2142
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:258150
Acceso en línea:https://ddd.uab.cat/record/258150
https://dx.doi.org/urn:doi:10.1007/s00018-022-04229-x
Access Level:acceso abierto
Palabra clave:RNase
Virus
RSV
Mirna
Trna
Trf
Descripción
Sumario: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.