Control of promoter utilization by bacteriophage T4-induced modification of RNA polymerase α subunit

Goldfarb, Alex; Palm, Peter

doi:10.1093/nar/9.19.4863

Cited by 28 publications

(14 citation statements)

References 37 publications

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“…It has long been known that purified T4‐modified RNA polymerase is much less efficient than the unmodified enzyme in transcribing bacteriophage T4 DNA in vitro , suggesting that one or more of these modifications is the cause of the early gene shut‐off. A number of studies aimed at understanding the molecular basis of this change in polymerase activity have involved core‐associated (ADP ribosylation and the RpbA protein) as well as sigma‐associated (AsiA) modifications (Seifert et al ., 1969; Khesin et al ., 1972; Stevens and Rhoton, 1975; Khesin et al ., 1976; Goldfarb, 1981; Goldfarb and Palm, 1981; Malik and Goldfarb, 1984; Drivdahl and Kutter, 1990). Our analysis with the double mutants shows that eliminating AsiA together with RpbA, Mod, MotB or MotA is without consequence for early gene shut‐off.…”

Section: Discussionmentioning

confidence: 99%

The bacteriophage T4 anti‐sigma factor AsiA is not necessary for the inhibition of early promoters in vivo

Pène

Uzan²

2000

Molecular Microbiology

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Bacteriophage T4 early promoters are utilized immediately after infection and are abruptly turned off 2–3 min later (at 30°C) when the middle promoters are activated. The viral early protein AsiA has been suspected to bring about this transcriptional switch: not only does it activate transcription at middle promoters in vivo and in vitro but it also shows potent anti‐σ70 activity in vitro, suggesting that it is responsible for the shut‐off of early transcription. We show here that after infection with a phage deleted for the asiA gene the inhibition of early transcription occurs to the same extent and with the same kinetics as in a wild‐type infection. Thus, another AsiA‐independent circuit efficiently turns off early transcription. The association of a mutation in asiA with a mutation in mod, rpbA, motA or motB has no effect on the inhibition of early promoters, showing that none of these phage‐encoded transcriptional regulators is necessary for AsiA‐independent shut‐off. It is not known whether AsiA is able to inhibit early promoters in vivo, but host transcription is strongly inhibited in vivo upon induction of AsiA from a multicopy plasmid.

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Section: Discussionmentioning

confidence: 99%

The bacteriophage T4 anti‐sigma factor AsiA is not necessary for the inhibition of early promoters in vivo

Pène

Uzan²

2000

Molecular Microbiology

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“…Several lines of evidence indicate that to do so, the phage upregulates expression of IF2 while downregulating expression of IF3, thus stimulating translation of leaderless mRNA [155, 156]. Another example is the well-studied E. coli -infecting T4 phage which encodes ADP-ribosyltransferases, like ModB, which ribosylates host proteins involved in translation [157, 158]. No evidence is available yet on their influence on translation.…”

Section: Phage-encoded Proteinsmentioning

confidence: 99%

Learning from Bacteriophages - Advantages and Limitations of Phage and Phage-Encoded Protein Applications

Drulis-Kawa

Majkowska-Skrobek²,

Maciejewska³

et al. 2012

CPPS

212

163

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The emergence of bacteria resistance to most of the currently available antibiotics has become a critical therapeutic problem. The bacteria causing both hospital and community-acquired infections are most often multidrug resistant. In view of the alarming level of antibiotic resistance between bacterial species and difficulties with treatment, alternative or supportive antibacterial cure has to be developed. The presented review focuses on the major characteristics of bacteriophages and phage-encoded proteins affecting their usefulness as antimicrobial agents. We discuss several issues such as mode of action, pharmacodynamics, pharmacokinetics, resistance and manufacturing aspects of bacteriophages and phage-encoded proteins application.

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“…These results support previous findings (60,73) that ADP-ribosylation catalyzed by Alt enhances transcription from T4 early promoters, possibly by outcompeting transcription initiated at host promoters. The ModA-catalyzed modification of host RNA polymerase prevents transcription from host promoters that carry an UP element (18,53) and from T4 early promoters (21). However, since residual transcription was observed on all templates after ModA modification of RNA polymerase and since the initially low transcription of E. coli DNA was hardly reduced upon modification (Table 2), we concluded that the ModA-induced modification is not sufficient to prevent host transcription.…”

Section: Discussionmentioning

confidence: 87%

“…It has been inferred that the differences in the molecular masses of gpAlt (76 kDa) and gpModA (23 kDa) might be responsible for the different approaches to the ␣ subunits. The ModAinduced ADP-ribosylation of ␣ subunits inhibits transcription from T4 early promoters (21). Host polymerase may thus be conditioned to interact with other T4-encoded transcription factors that may be active in the middle mode (14,27,28,68) or late transcription (26,74,75,76).…”

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confidence: 99%

ModA and ModB, Two ADP-Ribosyltransferases Encoded by Bacteriophage T4: Catalytic Properties and Mutation Analysis

Tiemann

Depping

Gineikiene³

et al. 2004

J Bacteriol

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Bacteriophage T4 encodes three ADP-ribosyltransferases, Alt, ModA, and ModB. These enzymes participate in the regulation of the T4 replication cycle by ADP-ribosylating a defined set of host proteins. In order to obtain a better understanding of the phage-host interactions and their consequences for regulating the T4 replication cycle, we studied cloning, overexpression, and characterization of purified ModA and ModB enzymes. Site-directed mutagenesis confirmed that amino acids, as deduced from secondary structure alignments, are indeed decisive for the activity of the enzymes, implying that the transfer reaction follows the Sn1-type reaction scheme proposed for this class of enzymes. In vitro transcription assays performed with Altand ModA-modified RNA polymerases demonstrated that the Alt-ribosylated polymerase enhances transcription from T4 early promoters on a T4 DNA template, whereas the transcriptional activity of ModA-modified polymerase, without the participation of T4-encoded auxiliary proteins for middle mode or late transcription, is reduced. The results presented here support the conclusion that ADP-ribosylation of RNA polymerase and of other host proteins allows initial phage-directed mRNA synthesis reactions to escape from host control. In contrast, subsequent modification of the other cellular target proteins limits transcription from phage early genes and participates in redirecting transcription to phage middle and late genes.Posttranslational ADP-ribosylation of proteins is catalyzed by ADP-ribosyltransferases (ADP-RTs), which have been identified in viral, bacterial, and eukaryotic systems. Transfer of the ADP-ribose moiety from the substrate NAD ϩ to a specific amino acid residue, frequently histidine or arginine within a target protein, modulates the activity of the acceptor. ADP-ribosylation changes the electrostatic potential of a target protein by introducing two phosphate groups and may affect protein-DNA as well as protein-protein interactions. ADP-RTs were initially discovered as the exotoxins of pathogenic bacteria. Therefore, most of our knowledge concerning these proteins has been gained by biochemical, genetic, and structural studies performed on bacterial toxins, such as those produced by Corynebacterium diphtheriae (15, 30), Bordetella pertussis (34), Vibrio cholerae (46), Pseudomonas aeruginosa (33), and Escherichia coli (45). New putative bacterial toxins were found to be encoded in the genomes of Streptococcus pyogenes and Salmonella enterica serovar Typhi (50).To date, the family of ADP-RTs comprises more than 40 enzymes, including bacterial exotoxins as well as a variety of other enzymes, such as the eukaryotic mono-and poly-ADPRTs, which include T-cell differentiation alloantigens like RT6 (9), poly-ADP-RTs (56), the dinitrogenase reductase regulation factor DraT (51,77), and enzymes encoded by T-even bacteriophages. The bacteriophage T4 gene products Alt (76 kDa), ModA (23 kDa), and ModB (24 kDa) appear to actively regulate gene expression during the transition from host t...

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Control of promoter utilization by bacteriophage T4-induced modification of RNA polymerase α subunit

Cited by 28 publications

References 37 publications

The bacteriophage T4 anti‐sigma factor AsiA is not necessary for the inhibition of early promoters in vivo

The bacteriophage T4 anti‐sigma factor AsiA is not necessary for the inhibition of early promoters in vivo

Learning from Bacteriophages - Advantages and Limitations of Phage and Phage-Encoded Protein Applications

ModA and ModB, Two ADP-Ribosyltransferases Encoded by Bacteriophage T4: Catalytic Properties and Mutation Analysis

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