Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Anti-viral defense by an ADP-ribosyltransferase that targets mRNA to block translation (RNA-Seq)

ABSTRACT: Host-pathogen conflicts are crucibles of molecular innovation. Selection for immunity to pathogens has driven the evolution of sophisticated immunity mechanisms throughout biology, including in bacteria that must evade their viral predators known as bacteriophages. Here, we characterize a toxin-antitoxin-chaperone system, CmdTAC, in Escherichia coli that provides robust defense against infection by T4 phage. During infection, newly synthesized capsid protein triggers dissociation of the chaperone CmdC from the CmdTAC complex, leading to destabilization and degradation of the antitoxin CmdA, with consequent liberation of the toxin CmdT, an ADP-ribosyltransferase. Strikingly, CmdT does not target a protein, DNA, or structured RNA, the known targets of other ADP-ribosyltransferases. Instead, CmdT modifies the N6 position of adenine in GA dinucleotides within single-stranded RNAs to robustly block mRNA translation and viral replication. Our work reveals both a new mechanism of anti-phage defense and a new class of ADP-ribosyltransferases that targets mRNA.

ORGANISM(S): Escherichia coli Escherichia phage T4

PROVIDER: GSE253513 | GEO | 2024/03/09

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Anti-viral defense by an ADP-ribosyltransferase that targets mRNA to block translation (RIP-Seq in vivo)

Project description:Host-pathogen conflicts are crucibles of molecular innovation. Selection for immunity to pathogens has driven the evolution of sophisticated immunity mechanisms throughout biology, including in bacteria that must evade their viral predators known as bacteriophages. Here, we characterize a toxin-antitoxin-chaperone system, CmdTAC, in Escherichia coli that provides robust defense against infection by T4 phage. During infection, newly synthesized capsid protein triggers dissociation of the chaperone CmdC from the CmdTAC complex, leading to destabilization and degradation of the antitoxin CmdA, with consequent liberation of the toxin CmdT, an ADP-ribosyltransferase. Strikingly, CmdT does not target a protein, DNA, or structured RNA, the known targets of other ADP-ribosyltransferases. Instead, CmdT modifies the N6 position of adenine in GA dinucleotides within single-stranded RNAs to robustly block mRNA translation and viral replication. Our work reveals both a new mechanism of anti-phage defense and a new class of ADP-ribosyltransferases that targets mRNA.

2024-03-09 | GSE253512 | GEO

Anti-viral defense by an ADP-ribosyltransferase that targets mRNA to block translation (RIP-Seq in vitro)

2024-03-09 | GSE253511 | GEO

A viral ADP-ribosyltransferase attaches RNA chains to host proteins

Project description: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 through ADP-ribosylation using nicotinamide adenine dinucleotide (NAD) as substrate. Recently, NAD was identified as a 5’-modification of cellular RNAs. Here, we report that T4 ART ModB accepts not only NAD but also NAD-capped RNA (NAD-RNA) as substrate and attaches entire RNA chains to acceptor proteins in an “RNAylation” reaction. ModB specifically RNAylates ribosomal proteins rS1 and rL2 at defined arginine residues, and selected E. coli and T4 phage RNAs are linked to rS1 in vivo. T4 phages that express an inactive mutant of ModB show a decreased burst size and slowed lysis of E. coli. Our findings reveal a distinct biological role of NAD-RNA, namely 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 exemplifies the first direct connection between RNA modification and post-translational protein modification. As ARTs play important roles far beyond viral infections, RNAylation may have far-reaching implications.

2023-05-25 | GSE214431 | GEO

A phage-encoded RNA-binding protein inhibits the antiviral activity of a toxin-antitoxin system

Project description:Bacteria harbor diverse mechanisms to defend themselves against their viral predators, bacteriophages. In response, phages can evolve counter-defense systems, most of which remain poorly understood. In T4-like phages, the gene tifA prevents bacterial defense by the type III toxin-antitoxin (TA) system toxIN, but the mechanism by which TifA inhibits toxIN remains unclear. Here, we show that TifA directly binds both the endoribonuclease ToxN and RNA, leading to the formation of a high molecular weight ribonucleoprotein complex in which ToxN is inhibited. The RNA binding activity of TifA is necessary for its interaction with and inhibition of ToxN. Thus, we propose that TifA inhibits ToxN during phage infection by trapping ToxN on cellular RNA, particularly the abundant 16S rRNA, preventing cleavage of phage transcripts. Taken together, our results reveal a novel mechanism underlying inhibition of a phage-defensive RNase toxin by a small, phage-encoded protein.

2023-12-04 | GSE234211 | GEO

Anti-viral defense by an ADP-ribosyltransferase that targets mRNA to block translation

Project description:Anti-viral defense by an ADP-ribosyltransferase that targets mRNA to block translation

| PRJNA1065921 | ENA

Mechanism of phage sensing and abortion by toxin-antitoxin-chaperone systems (HDX-MS)

Project description:Toxin-antitoxins (TAs) are prokaryotic two-gene systems comprised of a toxin neutralised by an antitoxin. Toxin-antitoxin-chaperone (TAC) systems additionally include a SecB-like chaperone that stabilises the antitoxin by recognising its chaperone addiction (ChAD) element. TACs have been shown to mediate antiphage defence, but the mechanisms of viral sensing and restriction are unexplored. Here we tried to find the epitope between SecB and gpV with HDX-MS.

2024-03-14 | PXD050182 | Pride

Retron-Eco1 assembles NAD+-hydrolyzing filaments that provide immunity against bacteriophages

Project description:Retrons are toxin-antitoxin systems protecting bacteria against bacteriophages via abortive infection. The Retron-Eco1 antitoxin is formed by a reverse transcriptase (RT) and a non-coding RNA (ncRNA)/multi-copy single-stranded DNA (msDNA) hybrid that neutralizes an uncharacterized toxic effector. Yet, the molecular mechanisms underlying phage defense remain unknown. Here, we show that the N-glycosidase effector, which belongs to the STIR superfamily, hydrolyzes NAD+ during infection. Cryoelectron microscopy (cryo-EM) analysis shows that the msDNA stabilizes a filament that cages the effector in a low-activity state in which ADPr, a NAD+ hydrolysis product, is covalently linked to the catalytic E106 residue. Mutations shortening the msDNA induce filament disassembly and the effector’s toxicity, underscoring the msDNA role in immunity. Furthermore, we discovered a phage-encoded Retron-Eco1 inhibitor (U56) that binds ADPr, highlighting the intricate interplay between retron systems and phage evolution. Our work outlines the structural basis of Retron-Eco1 defense, uncovering ADPr’s pivotal role in immunity.

2024-05-23 | PXD044835 | Pride

Anti-viral defense by an ADP-ribosyltransferase that targets mRNA to block translation (RNA-Seq)

Project description:Anti-viral defense by an ADP-ribosyltransferase that targets mRNA to block translation (RNA-Seq)

| PRJNA1065926 | ENA

A viral ADP-ribosyltransferase attaches RNA chains to host proteins

Project description: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.

2023-06-01 | PXD038910 | Pride

A viral ADP-ribosyltransferase attaches RNA chains to host proteins

Project description:A viral ADP-ribosyltransferase attaches RNA chains to host proteins

| PRJNA885396 | ENA