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bioRxiv · 10.1101/2025.05.30.656608

RNA binding regulation is a new dimension in the type I IFN response

Iselin, L.·Demyanenko, Y.·Palmalux, N.·Embarc Buh, A.·Kamel, W.·Simmonds, P.·Mohammed, S.·Castello, A.
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Abstract

The type I interferon (IFN-I) response shapes the intracellular environment to supress virus infection. Historically, this remodelling has been linked to the transcriptional induction of interferon stimulated genes (ISGs). However, IFN-I-driven post-translational regulation of proteins already present in the cell remains relatively unexplored. Here, we profiled the activity of cellular RNA-binding proteins (RBPs), which are key players in antiviral immunity. Using RNA interactome capture (RIC), we identified hundreds of RBPs whose association with RNA is regulated by IFN-I (IR-RBPs). Among these IR-RBPs are both known antiviral proteins and novel candidates identified in this study through a knockdown screen. By modifying RIC to study IR-RBPs phosphorylation states, we identified several putative instances of IFN-I-driven phospho-regulation of RNA binding. We experimentally confirmed this phospho-driven regulation for MATR3. Altogether, our results reveal a new dimension of the cells antiviral programme, in which the cellular RNA-bound proteome is remodelled by IFN-I.

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Iselin, L., Demyanenko, Y., Palmalux, N., Embarc Buh, A., Kamel, W., Simmonds, P., Mohammed, S., Castello, A.. 2025-05-30. RNA binding regulation is a new dimension in the type I IFN response. https://doi.org/10.1101/2025.05.30.656608

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