Joan Curcio
    Within yeast cells (left panel)
    Within yeast cells (left panel), Ty1 ribonucleoprotein complexes form cytoplasmic foci known as retrosomes. Retrosomes are visualized by fluorescent microscopy (right panel). Ty1 RNA (red signal) and Ty1-encoded proteins (green signal) co-localize in retrosomes, resulting in a yellow signal produced by overlapping red and green signals. Nuclear DNA is stained blue. Localization of retrotransposon components in retrosomes is hypothesized to promote the formation of replication-competent virus-like particles.

Joan Curcio, Ph.D.

Host-Retrotransposon Interactions
Professor, Biomedical Sciences, School of Public Health
Ph.D., George Washington University (1987)
Postdoctoral Fellow, National Cancer Institute-Frederick Cancer Research Center
(518) 473-4213
Fax: (518) 474-3181

Research Interests

There is no cure for diseases caused by retroviruses such as HIV-1, the infectious agent that has given rise to the human AIDS pandemic. Antiretroviral therapies can slow the progression of HIV/AIDS, but their usefulness is limited by their toxicity to human cells. The goal of our research is to identify highly specific targets for antiretroviral therapies by identifying replication mechanisms that are conserved among retroviruses and related endogenous retrotransposons but unnecessary for host cell replication or survival.

Long-terminal repeat (LTR) retrotransposons are mobile elements that have invaded nearly all eukaryotic genomes and given rise to infectious retroviruses. A conserved feature of retrovirus and LTR-retrotransposon replication is the use of a trifunctional mRNA that encodes essential replication proteins, is packaged within viral or virus-like particles and is reverse transcribed into a DNA copy. In contrast, cellular mRNAs rarely serve functions beyond encoding proteins. Therefore, elucidating the cis-acting sequences and mechanisms involved in retroviral and retrotransposon RNA translation, localization, packaging and reverse transcription will identify RNA structural elements and protein:RNA interactions that could be specific targets for novel antiviral therapies. We use Ty LTR-retrotransposons in the yeast Saccharomyces cerevisiae as a model system for structural and functional analyses of retrotransposon/retrovirus RNA.

Our goals include solving the secondary and tertiary structure of Ty1 RNA and defining the RNA structural changes and RNA:protein interactions that govern the partitioning of Ty1 mRNA between its different functions in replication. Our studies in S. cerevisiae have generated an invaluable research tool to reach these goals: a collection of evolutionarily conserved host factors that are necessary for Ty1 RNA translation, packaging, localization or reverse transcription.

We use genetic, biochemical and cell biological approaches to examine the role of these host factors in retrotransposon replication. Together, these analyses of Ty1 RNA structure, function and interaction with host factors will identify unique features of retrotransposon and retrovirus replication that can be exploited to develop novel therapies for retroviral diseases.

Select Publications
Curcio MJ. Border collies of the genome: domestication of an autonomous retrovirus-like transposon. Curr Genet. 2019; 65 (1): 71-78. DOI: 10.1007/s00294-018-0857-1
Curcio MJ. Ty1 Retrotransposition Frequency Assay Using a Chromosomal Ty1his3AI or Ty1kanMXAI Element. Bio-protocol Bio101. 2018; e3004.
Salinero AC, Knoll ER, Zhu ZI, Landsman D, Curcio MJ, Morse RH. The Mediator co-activator complex regulates Ty1 retromobility by controlling the balance between Ty1i and Ty1 promoters. PLoS Genet. 2018; 14 (2): e1007232.
Gamache ER, Doh JH, Ritz J, Laederach A, Bellaousov S, Mathews DH, Curcio MJ. Structure-Function Model for Kissing Loop Interactions That Initiate Dimerization of Ty1 RNA. Viruses. 2017; 9 (5): pii: E93.
Palumbo RJ, Fuchs G, Lutz S, Curcio MJ. Paralog-Specific Functions of RPL7A and RPL7B Mediated by Ribosomal Protein or snoRNA Dosage in Saccharomyces cerevisiae. G3. 2017; 7 (2): 591-606.
Rose RE, Pazos MA 2nd, Curcio MJ, Fabris D. Global Epitranscriptomics Profiling of RNA Post-Transcriptional Modifications as an Effective Tool for Investigating the Epitranscriptomics of Stress Response. Mol Cell Proteomics. 2016; 15 (3): 932-44.