Chancellor's Professor, Microbiology & Molecular Genetics
School of Medicine

Chair, Microbiology & Molecular Genetics
School of Medicine

ICP27, regulatory protein, HSV-1, mRNA processing, RNA export, virus-host interactions

M&MG web page

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.

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.

Tunnicliffe RB, Hu WK, Wu MY, Levy C, Mould AP, McKenzie EA, Sandri-Goldin RM, Golovanov AP. Molecular Mechanism of SR Protein Kinase 1 Inhibition by the Herpes Virus Protein ICP27. 2019. mBio 10:e02551-19

Wang X, Hennig T, Whisnant AW, Erhard F, Friedel CC, Forouzmand E, Hu W, Erber L, Chen Y, Sandri-Goldin RM, Dölken L, Shi Y. 2020. Herpes simplex virus blocks host transcription termination via the bimodal activities of ICP27. Nature Communications 11(1):293

Xu X, Holmes TC, Luo M-H, Beier, KT, Zhao, F, Zeng W, Hui M, Semler BL, Sandri-Goldin RM. Viral vectors for neural circuit mapping and recent advances in trans-synaptic anterograde tracers. Neuron (2020) https://doi.org/10.1016/j.neuron.2020.07.010

Schloss PD, Junior M, Alvania R, Arias CA, Baumler A, Casadevall A, Detweiler C, Drake H, Gilbert J, Imperiale MJ, Lovett S, Maloy S, McAdam AJ, Newton ILG, Sadowsky MJ, Sandri-Goldin RM, Silhavy TJ, Tontonoz P, Young JH, Cameron CE, Cann I, Fuller AO, Kozik AJ. 2020. The ASM Journals Committee values the contributions of Black microbiologists. mBio. 2020 Jul 31;11(4):e01998-20.

National Institutes of Health-NIGMS “Herpes simplex virus-mediated regulation of host gene expression” co-PI R01GM128441- May 2018-March 2022

National Institutes of Health-NIMH “Genetically engineered anterograde monosynaptic viral tracers for multi-species neural circuit analysis” co-PI 1RF1MH120020-01- 08/15/2019 – 07/31/2022.

American Society for Microbiology

American Society for Virology

RNA Society

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

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https://faculty.uci.edu/profile/?facultyId=2246

Last updated
12/11/2020