Journal Article

The Phage-Encoded N-Acetyltransferase Rac Mediates Inactivation of Pseudomonas aeruginosa Transcription by Cleavage of the RNA Polymerase Alpha Subunit

Severinov, Konstantin, Xu, Hua, Hendrix, Hanne, Hedge, Subray, Akulenko, Natalia, Voet, Marleen, Landuyt, Bart, Blanchard, John, Wagemans, Jeroen, Paeshuyse, Jan, Lavigne, Rob, Klimuk, Evgeny, De Smet, Jeroen, Ceyssens, Pieter-Jan

2020

Overview

In this study, we describe the biological function of the phage-encoded protein RNA polymerase alpha subunit cleavage protein (Rac), a predicted Gcn5-related acetyltransferase encoded by phiKMV-like viruses. These phages encode a single-subunit RNA polymerase for transcription of their late (structure- and lysis-associated) genes, whereas the bacterial RNA polymerase is used at the earlier stages of infection. Rac mediates the inactivation of bacterial transcription by introducing a specific cleavage in the α subunit of the bacterial RNA polymerase. This cleavage occurs within the flexible linker sequence and disconnects the C-terminal domain, required for transcription initiation from most highly active cellular promoters. To achieve this, Rac likely taps into a novel post-translational modification (PTM) mechanism within the host Pseudomonas aeruginosa. From an evolutionary perspective, this novel phage-encoded regulation mechanism confirms the importance of PTMs in the prokaryotic metabolism and represents a new way by which phages can hijack the bacterial host metabolism.

• Publisher: MDPI AG,MDPI
• Subject: Acetyltransferase / acetyltransferases / Acetyltransferases - genetics / Acetyltransferases - metabolism / amino acid sequences / Amino acids / Bacteria / Bacterial Proteins - genetics / Bacterial Proteins - metabolism / bacteriophages / Binding sites / Cell culture / Deoxyribonucleic acid / DNA / DNA-directed RNA polymerase / DNA-Directed RNA Polymerases - genetics / DNA-Directed RNA Polymerases - metabolism / E coli / Enzymes / Genes / Glycerol / host transcriptional shutdown / Host-Pathogen Interactions / Infections / Kinases / Lysis / N-Acetyltransferase / Nucleotide sequence / phage-induced acetylation / Phages / phage–host interactions / Post-translation / post-translational modification / Protein expression / Proteins / Pseudomonas aeruginosa / Pseudomonas aeruginosa - enzymology / Pseudomonas aeruginosa - genetics / Pseudomonas aeruginosa - virology / Pseudomonas Phages - enzymology / Pseudomonas Phages - genetics / RNA phages / RNA polymerase / Transcription initiation / Transcription, Genetic / Viral Proteins - genetics / Viral Proteins - metabolism