The gammaherpesviral TATA-box-binding protein directly interacts with the CTD of host RNA Pol II to direct late gene transcription
Journal Article
·
· PLoS Pathogens
- Univ. of California, Berkeley, CA (United States). Dept. of Plant and Microbial Biology; OSTI
- Univ. of California, Berkeley, CA (United States). Dept. of Plant and Microbial Biology
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Molecular Biophysics and Integrative Bio-Imaging Division; Univ. of California, Berkeley, CA (United States). Biophysics Graduate Group
- Univ. of California, Berkeley, CA (United States). Dept. of Molecular and Cell Biology
- Univ. of California, Berkeley, CA (United States). School of Public Health. Division of Infectious Diseases and Immunity
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Molecular Biophysics and Integrative Bio-Imaging Division; Univ. of California, Berkeley, CA (United States). Dept. of Molecular and Cell Biology. California Institute for Quantitative Biosciences (QB3). Howard Hughes Medical Inst.
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.
- Research Organization:
- Univ. of California, Berkeley, CA (United States)
- Sponsoring Organization:
- USDOE Office of Science (SC)
- Grant/Contract Number:
- AC02-05CH11231
- OSTI ID:
- 1815988
- Journal Information:
- PLoS Pathogens, Journal Name: PLoS Pathogens Journal Issue: 9 Vol. 16; ISSN 1553-7374
- Publisher:
- Public Library of ScienceCopyright Statement
- Country of Publication:
- United States
- Language:
- English
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