title: Proteomic and phylogenetic coevolution analyses of pM79 and pM92 identify interactions with RNA polymerase II and delineate the murine cytomegalovirus late transcription complex.
abstract: The regulation of the late viral gene expression in betaherpesviruses is largely undefined. We have previously shown that the murine cytomegalovirus proteins pM79 and pM92 are required for late gene transcription. Here, we provide insight into the mechanism of pM79 and pM92 activity by determining their interaction partners during infection. Co-immunoprecipitation-coupled MS studies demonstrate that pM79 and pM92 interact with an array of cellular and viral proteins involved in transcription. Specifically, we identify RNA polymerase II as a cellular target for both pM79 and pM92. We use inter-protein coevolution analysis to show how pM79 and pM92 likely assemble into a late transcription complex composed of late transcription regulators pM49, pM87 and pM95. Combining proteomic methods with coevolution computational analysis provides novel insights into the relationship between pM79, pM92 and RNA polymerase II and allows the generation of a model of the multi-component viral complex that regulates late gene transcription.
authors.affiliation: Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA.|Division of Pediatric Rheumatology, Department of Pediatrics, Washington University School of Medicine, Saint Louis, MO 63110, USA.|Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Travis J
authors.initials: TJ
authors.lastname: Chapa
authors.affiliation: Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Yushen
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Ren
authors.initials: R
authors.lastname: Sun
authors.affiliation: Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Dong
authors.initials: D
authors.lastname: Yu
authors.affiliation: Division of Pediatric Rheumatology, Department of Pediatrics, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Anthony R
authors.initials: AR
authors.lastname: French
mesh_terms: D000818:Animals; D019143:Evolution, Molecular; D015967:Gene Expression Regulation, Viral; D047468:Immunoprecipitation; D051379:Mice; D018146:Muromegalovirus / Q000145:classification / Q000235:genetics*; D010802:Phylogeny; D040081:Protein Array Analysis; D040901:Proteomics; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D054334:Viral Regulatory and Accessory Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*
chemical_list: D014157:Transcription Factors; D054334:Viral Regulatory and Accessory Proteins; D012319:RNA Polymerase II