Rozanne M. Sandri-Goldin
Microbiology & Molecular Genetics, School of Medicine
Phone: (949) 824-7570
Email: rmsandri@uci.edu
http://www.faculty.uci.edu/profile.cfm?faculty_id=2246
www.ucihs.uci.edu/microbio/
Rozanne Sandri-Goldin
Dr. Sandri-Goldin is studying the ICP27 protein of herpes simplex virus type 1 (HSV-1). Immediate earlyprotein ICP27 is a multifunctional regulator of gene expression that assumes different roles during the course of infection. Early in infection, ICP27 mediates the inhibition of cellular splicing, whereas, later it helps to recruit cellular RNA polymerase II (RNAP II) to viral replication sites and it facilitates viral RNA export. It has also been suggested to be involved in stimulating translation of viral transcripts. ICP27 performs its activities by interacting with RNA and with an assortment of proteins. ICP27 binds viral RNAs in its role as an export adaptor. An ever increasing number of cellular proteins also have been shown to interact with ICP27, including splicing factors, export proteins and RNAP II. Thus, ICP27 appears to be intimately associated with cellular and viral RNA metabolism from transcription and processing through export to the cytoplasm and translation. Determining the mechanisms of its actions and how its diverse functions are coordinately regulated is important for understanding the dynamics of HSV-1 lytic infection and viral take-over of the host cell.
ICP27 is the only HSV-1 IE protein that has homologues in all of the human herpesviruses and throughout the herpesvirus family. When studies have been performed on these homologues, functions similar to those described for ICP27 have been found. For example, Epstein-Barr virus (EBV) SM protein (also called EB2 and Mta) has been shown to shuttle between the nucleus and cytoplasm; to mediate the cytoplasmic accumulation of EBV gene transcripts; to enhance processing of an EBV transcript; to affect RNA splicing, and to associate with a splicing factor. Similarly, ORF 57 of herpesvirus saimiri functions post-transcriptionally and interacts with a splicing factor. Other ICP27 homologues have also been shown to function post-transcriptionally, including UL69 of human cytomegalovirus (HCMV) and ORF57 of Kaposi’s sarcoma herpes virus (KSHV). Further, SM and ORF57 have been shown to interact with cellular RNA export proteins, similar to ICP27, and to facilitate viral RNA export. The activities and required domains of ICP27 homologs have only begun to be defined, whereas much is known about the required domains and interactions of ICP27. In current studies, they are striving to define the structure of the functional domains of ICP27 and to elucidate the dynamics of its intermolecular interactions. In future studies, they plan to probe how the human herpesvirus ICP27 homologues, EBV SM and KSHV ORF57 perform their roles during infection of these oncogenic viruses. While they share some sequence homology with ICP27, the functions of these proteins have been only partially defined. Domain swap experiments that are intelligently designed based on the structural knowledge of ICP27 functional domains can help to elucidate the roles of these homologues in future studies.
Selected Publications:
Sciabica, K. S., Dai, Q. J., and Sandri-Goldin, R. M. (2003). ICP27 interacts with SRPK1 to mediate HSV splicing inhibition by altering SR protein phosphorylation. Embo J 22(7), 1608-19.
Sun, A., Devi-Rao, G. V., Rice, M. K., Gary, L. W., Bloom, D. C., Sandri-Goldin, R. M., Ghazal, P., and Wagner, E. K. (2004). Immediate-early expression of the herpes simplex virus type 1 ICP27 transcript is not critical for efficient replication in vitro or in vivo. J Virol 78(19), 10470-8.
Chen, I. H., Li, L., Silva, L., and Sandri-Goldin, R. M. (2005). ICP27 recruits Aly/REF but not TAP/NXF1 to herpes simplex virus type 1 transcription sites although TAP/NXF1 is required for ICP27 export. J Virol 79(7), 3949-61.
Dai-Ju, J. Q., Li, L., Johnson, L. A., and Sandri-Goldin, R. M. (2006). ICP27 interacts with the C-terminal domain of RNA polymerase II and facilitates its recruitment to herpes simplex virus 1 transcription sites, where it undergoes proteasomal degradation during infection. J Virol 80(7), 3567-81.
Kang, W., Mukerjee, R., Gartner, J. J., Hatzigeorgiou, A. G., Sandri-Goldin, R. M., and Fraser, N. W. (2006). Characterization of a spliced exon product of herpes simplex type-1 latency-associated transcript in productively infected cells. Virology 356(1-2), 106-14.
Li, L., Johnson, L. A., Dai-Ju, J. Q., and Sandri-Goldin, R. M. (2008). Hsc70 focus formation at the periphery of HSV-1 transcription sites requires ICP27. PLoS ONE 3(1), e1491. |
