RNAylation is a recently identified post-translational modification where NAD-capped RNAs are covalently attached to host proteins, catalyzed by the ADP-ribosyltransferase ModB of T4 bacteriophage. Traditionally, ADP-ribosylation was the only known modification of this kind, involving the transfer of an ADP-ribose group from NAD to a protein acceptor. In contrast, RNAylation involves the attachment of NAD-RNA molecule to ribosomal proteins, such as rL2 and rS1, which are key players in translation initiation and elongation (1). However, the biological role of RNAylation in translation remains elusive. Interestingly, T4-infected Escherichia coli cells with a catalytically inactive ModB show phenotypic changes, including delayed lysis, smaller burst size, and reduced phage adsorption (2), suggesting ModB"s critical role in modulating the translational machinery during infection. This study aims to investigate the impact of RNAylation on ribosomal proteins and translation.

Understanding these mechanisms will enhance our knowledge of how RNAylation modulates translation during viral infections, new insights into translation regulation and valuable comprehension in manipulating viral replication and host responses.

(1) Demirel, N.Y., Weber, M., Höfer, K. Bridging the gap: RNAylation conjugates RNAs to proteins. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1871(8), 2024

(2) Wolfram-Schauerte, M., Pozhydaieva, N., Grawenhoff, J., et al. A viral ADP-ribosyltransferase attaches RNA chains to host proteins. Nature, 620, 1054–1062 (2023).