Updated project metadata.
The mechanisms by which viruses hijack their host’s genetic machinery are of current interest. When bacteriophage T4 infects Escherichia coli, three different ARTs (ADP-ribosyltransferases) reprogram the host’s transcriptional and translational apparatus 1,2 through ADP-ribosylation using nicotinamide adenine dinucleotide (NAD) as substrate. Recently, NAD was identified as a 5’-modification of cellular RNAs 3-5. Here, we report that the bacteriophage T4 ART ModB accepts not only NAD but also NAD-capped RNA (NAD-RNA) as substrate, linking entire RNA chains to acceptor proteins in an “RNAylation” reaction. We discovered that ModB specifically RNAylates ribosomal proteins rS1 and rL2. By mass spectrometric (MS) analysis we identified arginine residues of rS1 and rL2 as RNAylation sites. Furthermore, we identified specific E. coli and T4 phage RNAs, which are covalently linked to rS1 in vivo. T4 phages expressing an inactive mutant of ModB show a decreased burst size and a decelerated lysis of E. coli during T4 infection. The attachment of specific RNAs to ribosomal proteins might provide a strategy for the phage to modulate the host’s translation machinery. Our findings reveal a distinct biological role of NAD-RNA, namely activation of the RNA for enzymatic transfer. This work exemplifies the first direct connection between RNA modification and post-translational protein modification. As ARTs play important roles far beyond viral infections 6, RNAylation may have far-reaching implications.