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You are here: Home / Teams / RNA metabolism in immunity and infection (RMI2) - E. Ricci / Publications / Stable structures or PABP1 loading protects cellular and viral RNAs against ISG20-mediated decay.

Stable structures or PABP1 loading protects cellular and viral RNAs against ISG20-mediated decay.

Camille Louvat, Séverine Deymier, Xuan-Nhi Nguyen, Emmanuel Labaronne, Kodie Noy, Marie Cariou, Antoine Corbin, Mathieu Mateo, Emiliano P Ricci, Francesca Fiorini, and Andrea Cimarelli (2024)

Life Sci Alliance, 7(5).

ISG20 is an IFN-induced 3'-5' RNA exonuclease that acts as a broad antiviralfactor. At present, the features that expose RNA to ISG20 remain unclear,although recent studies have pointed to the modulatory role of epitranscriptomicmodifications in the susceptibility of target RNAs to ISG20. These findings raisethe question as to how cellular RNAs, on which these modifications are abundant,cope with ISG20. To obtain an unbiased perspective on this topic, we used RNA-seqand biochemical assays to identify elements that regulate the behavior of RNAsagainst ISG20. RNA-seq analyses not only indicate a general preservation of thecell transcriptome, but they also highlight a small, but detectable, decrease inthe levels of histone mRNAs. Contrarily to all other cellular ones, histone mRNAsare non-polyadenylated and possess a short stem-loop at their 3' end, promptingus to examine the relationship between these features and ISG20 degradation. Theresults we have obtained indicate that poly(A)-binding protein loading on the RNA3' tail provides a primal protection against ISG20, easily explaining the overallprotection of cellular mRNAs observed by RNA-seq. Terminal stem-loop RNAstructures have been associated with ISG20 protection before. Here, were-examined this question and found that the balance between resistance andsusceptibility to ISG20 depends on their thermodynamic stability. These resultsshed new light on the complex interplay that regulates the susceptibility ofdifferent classes of viruses against ISG20.

 
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