Endonucleolytic RNA cleavage drives changes in gene expression during the innate immune response.
Cell Rep
; 43(6): 114287, 2024 Jun 25.
Article
in En
| MEDLINE
| ID: mdl-38823018
ABSTRACT
Viral infection triggers several double-stranded RNA (dsRNA) sensors that lead to changes in gene expression in the cell. One of these sensors activates an endonuclease, ribonuclease L (RNase L), that cleaves single-stranded RNA. However, how the resultant widespread RNA fragmentation affects gene expression is not fully understood. Here, we show that this fragmentation induces the ribotoxic stress response via ZAKα, potentially through stalled ribosomes and/or ribosome collisions. The p38 and JNK pathways that are activated as part of this response promote outcomes that inhibit the virus, such as programmed cell death. We also show that RNase L limits the translation of stress-responsive genes. Intriguingly, we found that the activity of the generic endonuclease, RNase A, recapitulates many of the same molecular phenotypes as activated RNase L, demonstrating how widespread RNA cleavage can evoke an antiviral program.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Endoribonucleases
/
Immunity, Innate
Limits:
Animals
/
Humans
Language:
En
Journal:
Cell Rep
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: