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Nature ; 620(7976): 1054-1062, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37587340

RESUMO

The mechanisms by which viruses hijack the genetic machinery of the cells they infect are of current interest. When bacteriophage T4 infects Escherichia coli, it uses three different adenosine diphosphate (ADP)-ribosyltransferases (ARTs) to reprogram the transcriptional and translational apparatus of the host by ADP-ribosylation using nicotinamide adenine dinucleotide (NAD) as a substrate1,2. NAD has previously been identified as a 5' modification of cellular RNAs3-5. Here we report that the T4 ART ModB accepts not only NAD but also NAD-capped RNA (NAD-RNA) as a substrate and attaches entire RNA chains to acceptor proteins in an 'RNAylation' reaction. ModB specifically RNAylates the ribosomal proteins rS1 and rL2 at defined Arg residues, and selected E. coli and T4 phage RNAs are linked to rS1 in vivo. T4 phages that express an inactive mutant of ModB have a decreased burst size and slowed lysis of E. coli. Our findings reveal a distinct biological role for NAD-RNA, namely the activation of the RNA for enzymatic transfer to proteins. The attachment of specific RNAs to ribosomal proteins might provide a strategy for the phage to modulate the host's translation machinery. This work reveals a direct connection between RNA modification and post-translational protein modification. ARTs have important roles far beyond viral infections6, so RNAylation may have far-reaching implications.


Assuntos
ADP Ribose Transferases , Bacteriófago T4 , Proteínas de Escherichia coli , Escherichia coli , NAD , RNA , Proteínas Virais , ADP Ribose Transferases/metabolismo , Bacteriófago T4/enzimologia , Bacteriófago T4/genética , Bacteriófago T4/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Escherichia coli/virologia , NAD/metabolismo , Proteínas Ribossômicas/química , Proteínas Ribossômicas/metabolismo , Proteínas Virais/metabolismo , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/metabolismo , RNA/química , RNA/genética , RNA/metabolismo , Biossíntese de Proteínas , Regulação Bacteriana da Expressão Gênica , Processamento de Proteína Pós-Traducional
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