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RNase L activation in the cytoplasm induces aberrant processing of mRNAs in the nucleus

Authors :
James M. Burke
Nina Ripin
Max B. Ferretti
Laura A. St Clair
Emma R. Worden-Sapper
Fernando Salgado
Sara L. Sawyer
Rushika Perera
Kristen W. Lynch
Roy Parker
Source :
PLOS Pathogens. 18:e1010930
Publication Year :
2022
Publisher :
Public Library of Science (PLoS), 2022.

Abstract

The antiviral endoribonuclease, RNase L, is activated by the mammalian innate immune response to destroy host and viral RNA to ultimately reduce viral gene expression. Herein, we show that RNase L and RNase L-mediated mRNA decay are primarily localized to the cytoplasm. Consequently, RNA-binding proteins (RBPs) translocate from the cytoplasm to the nucleus upon RNase L activation due to the presence of intact nuclear RNA. The re-localization of RBPs to the nucleus coincides with global alterations to RNA processing in the nucleus. While affecting many host mRNAs, these alterations are pronounced in mRNAs encoding type I and type III interferons and correlate with their retention in the nucleus and reduction in interferon protein production. Similar RNA processing defects also occur during infection with either dengue virus or SARS-CoV-2 when RNase L is activated. These findings reveal that the distribution of RBPs between the nucleus and cytosol is dictated by the availability of RNA in each compartment. Thus, viral infections that trigger RNase L-mediated cytoplasmic RNA in the cytoplasm also alter RNA processing in the nucleus, resulting in an ingenious multi-step immune block to protein biogenesis.

Details

ISSN :
15537374
Volume :
18
Database :
OpenAIRE
Journal :
PLOS Pathogens
Accession number :
edsair.doi.dedup.....784668b3e77531c31569d1f4ac4af99f
Full Text :
https://doi.org/10.1371/journal.ppat.1010930