RNA polymerase II holoenzyme modifications accompany transcription reprogramming in herpes simplex virus type 1-infected cells.
During lytic infection, herpes simplex virus type 1 (HSV-1) represses host transcription, recruits RNA polymerase II (RNAP II) to viral replication compartments, and alters the phosphorylation state of the RNAP II large subunit. Host transcription repression and RNAP II modifications require expression of viral immediate-early (IE) genes. Efficient modification of the RNAP II large subunit to the intermediately phosphorylated (IIi) form requires expression of ICP22 and the UL13 kinase. We have further investigated the mechanisms by which HSV-1 effects global changes in RNAP II transcription by analyzing the RNAP II holoenzyme. We find that the RNAP II general transcription factors (GTFs) remain abundant after infection and are recruited into viral replication compartments, suggesting that they continue to be involved in viral gene transcription. However, virus infection modifies the composition of the RNAP II holoenzyme, in particular triggering the loss of the essential GTF, TFIIE. Loss of TFIIE from the RNAP II holoenzyme requires viral IE gene expression, and viral IE proteins may be redundant in mediating this effect. Although viral IE proteins do not associate with the RNAP II holoenzyme, they interact with RNAP II in complexes of lower molecular mass. As the RNAP II holoenzyme containing TFIIE is necessary for activated transcription initiation and RNAP II large subunit phosphorylation in uninfected cells, virus-induced modifications to the holoenzyme may affect both of these processes, leading to aberrant phosphorylation of the RNAP II large subunit and repression of host gene transcription.
Jenkins
H L
HL
Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, Alberta T6G 1Z2, Canada.
Spencer
C A
CA
D006367:HeLa Cells; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000502:physiology*; D020035:Holoenzymes / Q000378:metabolism; D006801:Humans; D017874:Immediate-Early Proteins / Q000032:analysis / Q000378:metabolism; D010766:Phosphorylation; D012319:RNA Polymerase II / Q000737:chemistry / Q000378:metabolism*; D014157:Transcription Factors / Q000032:analysis / Q000378:metabolism; D019473:Transcription Factors, TFII; D014158:Transcription, Genetic; D014779:Virus Replication
D020035:Holoenzymes; D017874:Immediate-Early Proteins; D014157:Transcription Factors; D019473:Transcription Factors, TFII; C066644:transcription factor TFIIE; D012319:RNA Polymerase II