Open AccessThe gammaherpesviral TATA-box-binding protein directly interacts with the CTD of host RNA Pol II to direct late gene transcription
Author(s) -
Angelica F. Castañeda,
Allison L. Didychuk,
Robert K. Louder,
Chloe O. McCollum,
Zoe H. Davis,
Eva Nogales,
Britt A. Glaunsinger
Publication year - 2020
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1008843
Subject(s) - rna polymerase ii , transcription factor ii d , biology , tata box binding protein , transcription preinitiation complex , transcription factor ii e , transcription (linguistics) , tata box , microbiology and biotechnology , tata binding protein , transcription factor ii f , general transcription factor , transcription factor ii b , gene , virology , promoter , genetics , gene expression , linguistics , philosophy
β- and γ-herpesviruses include the oncogenic human viruses Kaposi’s sarcoma-associated virus (KSHV) and Epstein-Barr virus (EBV), and human cytomegalovirus (HCMV), which is a significant cause of congenital disease. Near the end of their replication cycle, these viruses transcribe their late genes in a manner distinct from host transcription. Late gene transcription requires six virally encoded proteins, one of which is a functional mimic of host TATA-box-binding protein (TBP) that is also involved in recruitment of RNA polymerase II (Pol II) via unknown mechanisms. Here, we applied biochemical protein interaction studies together with electron microscopy-based imaging of a reconstituted human preinitiation complex to define the mechanism underlying Pol II recruitment. These data revealed that the herpesviral TBP, encoded by ORF24 in KSHV, makes a direct protein-protein contact with the C-terminal domain of host RNA polymerase II (Pol II), which is a unique feature that functionally distinguishes viral from cellular TBP. The interaction is mediated by the N-terminal domain (NTD) of ORF24 through a conserved motif that is shared in its β- and γ-herpesvirus homologs. Thus, these herpesviruses employ an unprecedented strategy in eukaryotic transcription, wherein promoter recognition and polymerase recruitment are facilitated by a single transcriptional activator with functionally distinct domains.