Transcriptional reprogramming by bacteriophage T4: turning the host transcriptional machinery to the dark side

Immediately after infection of Escherichia coli, bacteriophage T4 begins to reprogram the host's transcriptional machinery, first by chemical modification and then by producing factors that alter the specificity of RNA polymerase (RNAP). This leads to the temporal expression of three classes of T4 transcripts: early, middle, and late. For early transcription, the Alt protein, which is present in the phage head, is injected with the DNA and subsequently ADP-ribosylates RNAP, providing an advantage for T4 early promoters over host promoters. For middle and late transcription, T4 utilizes phage-encoded factors to either reconfigure or replace the primary specificity subunit, σ⁷⁰, of RNAP, respectively. In both cases, the phage relies on several processes to maximize the efficiency of these phage-created, alternative σ's. This review summarizes older biochemical, genetic, and structural work that elucidated many of the elegant mechanisms of this transcriptional takeover and focuses on the more recent cryo-EM structures of the complete transcription machines that allow us to visualize the processes.