ICP27, regulatory protein, HSV-1, mRNA processing, RNA export, virus-host interactions
NIH Research Career Development Award
Athalie Clark Award
NIH MERIT Award
Elected to the American Academy of Microbiology
President of the American Society for Virology, 2009-2010
Chair, Gordon Research Conference on Viruses and Cells, Barga, Italy
Elected Fellow of the American Association for the Advancement of Science (AAAS)
Subak-Sharpe Lecturer at the 31st International Herpesvirus Workshop
Keynote Lecturer, 4th European Congress of Virology, Cerrnobio, Italy
Division S Lecturer, DNA Viruses, American Society for Microbiology 2011
Meeting, New Orleans
Keynote Lecturer, Chinese Virology Society Meeting, Xi’an, China
Harold Ginsberg Lecturer, 35th American Society for Virology Meeting
Chancellor's Professor, School of Medicine
Editor, Journal of Virology, 2001-2010
Editorial Board, Virology 1998-2016
Editor, mBio 2010-2019
Editorial Board,Current Opinion in Virology 2010-present
Editor-in-Chief, Journal of Virology, 2012-2022
The studies in my lab are focused on a multifunctional regulatory protein of herpes simplex virus (HSV-1) termed ICP27. ICP27 is required for all stages of viral gene expression from transcription through RNA processing and export to translation. It performs these many functions by interacting with a number of cellular proteins and by binding viral RNA. ICP27 mediates the inhibition of host cell pre-mRNA splicing, which contributes to the shut-off of host protein synthesis. ICP27 recruits cellular RNA polymerase II to viral sites of transcription/replication to promote efficient viral transcription. ICP27 recruits cellular mRNA export proteins to viral transcription/replication sites to facilitate efficient viral RNA export. ICP27 itself binds viral RNA and directs it to the TAP/NXF1 mRNA export receptor and accompanies the mRNP through the nuclear pore complex to the cytoplasm, where it then recruits translation initiation factors to stimulate translation of viral transcripts.
We are directing our studies toward a structural analysis of ICP27 and the creation of targeted mutations to determine the structure-function of ICP27 interactions.
Johnson, L.A. and R.M. Sandri-Goldin. 2009. Efficient nuclear export of herpes simplex virus 1 transcripts requires both RNA binding by ICP27 and ICP27 interaction with TAP/NXF1. J. Virol. 83:1184-1192, doi:10.1128/JVI.02010-08.
Souki, S.K., P.D. Gershon and R.M. Sandri-Goldin. 2009. Arginine methylation of the ICP27 RGG box regulates ICP27 export and is required for efficient herpes simplex virus 1 replication. J. Virol. 83:5309-5320, doi:10.1128/JVI.00238-09.
Johnson. L.A., L. Li and R.M. Sandri-Goldin. 2009. The cellular RNA export receptor TAP/NXF1 is required for ICP27- mediated export of herpes simplex virus 1 RNA, whereas, the TREX-complex adaptor protein Aly/REF appears to be dispensable.J. Virol. 83:6335-6346, doi:10.1128/JVI.00375-09.
Souki, S.K. and R.M. Sandri-Goldin. 2009. Arginine methylation of the ICP27 RGG box regulates the functional interactions of ICP27 with SRPK1 and Aly/REF during herpes simplex virus 1 infection. J. Virol. 83: 8970-8975, doi:10.1128/JVI.00801-09.
Corbin-Lickfett, K.A., I.B. Chen, M.J. Coco and R.M. Sandri-Goldin. 2009. The HSV-1 ICP27 RGG box specifically binds flexible G-C-rich sequences but not G-quartet structures. Nucleic Acids Res. doi:10.1093/nar/gkp793.
Rojas, S., Corbin-Lickfett, K.A., L. Escudero-Paunetto and R.M. Sandri-Goldin. 2010. ICP27 phosphorylation site mutants are defective in herpes simplex virus 1 replication and gene expression. J. Virol. 84:2200-2211. doi:10.1128/JVI.00917-09
Corbin-Lickfett, K.A., S. Rojas, L. Li, M.J. Cocco, and R.M. Sandri-Goldin. 2010. ICP27 phosphorylation site mutants display altered functional interactions with cellular export factors Aly/REF and TAP/NXF1 but are able to bind herpes simplex virus 1 RNA. J. Virol. 84:2212-2222. doi:10.1128/JVI.01388-09.
Escudero-Paunetto, L. L. Li, F.P. Hernadez and R.M. Sandri-Goldin. 2010. SR proteins SRp20 and 9G8 contribute to efficient export of herpes simplex virus 1 mRNAs. Virology 401:155-164. doi:10.1016/j.virol.2010.02.023
Hernandez, F.P. and R.M. Sandri-Goldin. 2010. Herpes simplex virus 1 regulatory protein ICP27 undergoes a head-to-tail intramolecular interaction. J. Virol. 84:4124-4135 doi:10.1128/JVI.02319-09
Corbin-Lickfett, K.A., S.K. Souki, M.J. Cocco and R.M. Sandri-Goldin. 2010. Three arginine residues within the RGG-box are crucial for ICP27 binding to herpes simplex virus 1 GC-rich sequences and for efficient viral RNA export. J. Virol. 84:6367-6376. doi:10.1128/JVI.00509-10.
Hernandez, F. P., and R. M. Sandri-Goldin. 2010. Head-to-tail intramolecular interaction of herpes simplex virus type 1 regulatory protein ICP27 is important for its interaction with cellular mRNA export receptor TAP/NXF1. mBio 1(5):e00268-1
Souki, S.K., F.P. Hernandez and R.M. Sandri-Goldin. 2011. Arginine methylation of the RGG box does not appear to regulate ICP27 import during herpes simplex virus infection. J. Virol. 85:6809-6813. doi:10.1128/JVI.00679-11
Hernandez, F.P. and R.M. Sandri-Goldin. 2011. Bimolecular fluorescence complementation analysis to reveal protein interactions in herpes virus infected cells. Methods 55:182-187. doi:10.1016/j.ymeth.2011.07.003
Sandri-Goldin, R.M. 2011. The many roles of the highly interactive herpes simplex virus protein ICP27, a key regulator of infection. Future Microbiology.6:1261-1277.
Tian, X., G. Devi-Rao, A.P. Golovanov and R.M. Sandri-Goldin. 2013. The interaction of the cellular export adaptor protein Aly/REF with ICP27 contributes to the efficiency of herpes simplex virus 1 mRNA export. J. Virol. 87:7210-7217. doi: 10.1128/JVI.00738-13. PMCID: PMC3700301
Ou, M. and R.M. Sandri-Goldin. 2013. Inhibition of cdk9 during Herpes Simplex Virus 1 Infection Impedes Viral Transcription. PLoS ONE. 8(10): e79007 doi:10.1371/journal.pone.0079007 PMCID: PMC3799718
Christensen MH, Jensen SB, Miettinen JJ, Luecke S, Prabakaran, Reinert T, Mettenleiter T, Chen ZJ, Knipe DM, Sandri-Goldin RM, Enquist LW, Hartmann R, Mogensen TH, Rice SA, Nyman TA, Matikainen S & Paludan SR. 2016. HSV-1 ICP27 targets the TBK1-activated STING signalsome to inhibit virus-induced type I IFN expression. EMBO J. 2016 Jul 1;35(13):1385-99. doi: 10.15252/embj.201593458. PMC4931188
Tunnicliffe, R.B., M. Schacht, C. Levy, T.A. Jowitt, R.M. Sandri-Goldin and A.P. Golovanov. 2015. The structure of the folded domain from the signature multifunctional protein ICP27 from herpes simplex virus-1 reveals an intertwined dimer. Scientific Reports 5, 11234; doi: 10.1038/srep11234.
Tunnicliffe RB, Lockhart-Cairns MP , Levy C, Mould P, Jowitt TA, Sito H, Baldock C, Sandri-Goldin RM and Golovanov AP. The herpes viral transcription factor ICP4 forms a novel DNA recognition complex. Nucleic Acids Res. 2017
Tunnicliffe RB, Collins RF, Ruiz Nivia HD, Sandri-Goldin RM, Golovanov AP. The ICP27 Homology Domain of the Human Cytomegalovirus Protein UL69 Adopts a Dimer-of-Dimers Structure mBio. 2018 Jun 19;9(3). pii: e01112-18. doi: 10.1128/mBio.01112-18
Tunnicliffe RB, Tian X, Storer J, Sandri-Goldin RM, Golovanov AP. Overlapping motifs on the herpes viral proteins ICP27 and ORF57 mediate interactions with the mRNA export adaptors ALYREF and UIF. Scientific Reports. 2018. 8(1):15005. doi: 10.1038/s41598-018-33379-x.
Tunnicliffe RB, Levy C, Ruiz Nivia, H, Sandri-Goldin, RM, Golovanov, AP. Structural identification of conserved RNA binding sites in herpesvirus ORF57 homologs: Implications for PAN RNA recognition. Nucleic Acids Res. 2018, doi: 10.1093/nar/gky1181.
American Society for Microbiology
American Society for Virology
American Society for Cell Biology
American Society for Biochemistry and Molecular Biology
American Association for the Advancement of Science
Cellular and Molecular Biosciences
Center for Virus Research