Neurobiology, Protein-Nucleic Acid Interactions, Regulation of Gene Expression
Disease Research Interests
Neurological and Behavioral Disorders
Molecular basis of disease, post-translational modifications, regulation of RNA expression, RNA-protein interactions
The human brain is made up of billions of specialized cells called neurons that act together to drive behavior, learning and memory through incompletely defined mechanisms. Neurons communicate with each other through their long cellular extensions that are composed of proteins. Proteins are encoded by messenger RNAs (mRNAs), which are copies of genes encoded by the hereditary material DNA. mRNAs are the recipes for proteins that are made in the cell and give the cell its unique identity. The subject of our current research is a recently characterized protein, RNA helicase MOV10, which is a cofactor of the microRNA pathway protein AGO2 and also of the Fragile X protein FMRP. We demonstrated that MOV10 is necessary for early embryonic development across species and for normal neuron development that includes producing the branches that connect neurons. The goals of our work are to identify the mRNAs that MOV10 unwinds, to understand how MOV10’s unwinding activity is regulated by modification and/or associated proteins and to determine how MOV10 participates in the production of the dendritic branching that is critical for neuronal function.
Bursts of protein translation are required for normal development and neuronal function but it is unknown how this process is regulated. The goal of our research is to explore the key role of RNA unwinding on RNA fate. The RNA helicase MOV10 binds in proximity to MicroRNA Recognition Elements (MREs) in 3’UTRs. It unwinds secondary structures in the RNA to allow access of the primary effector protein of the miRNA pathway, AGO2, to MREs. Using individual nucleotide Crosslinking Immunoprecipitation (iCLIP), we showed that MOV10 binds mRNAs encoding neuronal projection and cytoskeletal proteins in developing mouse brain, suggesting a role for MOV10 in regulating translation in dendrites. The hypothesis being tested is that MOV10 binds RNA G-quadruplexes (GQs), which are stable RNA secondary structures, to modulate AGO2 association to MREs in the 3’UTR. We have created a number of engineered mouse lines that allow us to explore MOV10’s role in brain development and behavior.
B.S., University of Wisconsin-Madison (Bacteriology)
Ph.D., University of Wisconsin-Madison (Genetics)
Postdoctoral fellow, University of Chicago
Postdoctoral fellow, Emory University
Nawaz, A., Kenny, P. J., Shilikbay, T., Reed, M., Stuchlik, O., Pohl, J., Ceman, S. 2023. Serine 970 of RNA helicase MOV10 is phosphorylated and controls unfolding activity and fate of AGO2 target mRNAs. J. Biological Chemistry, doi: 10.1016
Lannom, M.C., Nielsen, J., Nawaz, A., Shilikbay, T. and Ceman, S. 2021. FMRP and MOV10 regulate Dicer1 expression and dendrite development PLOS ONE
Nawaz, A., Shilikbay, T., Skariah, G. and Ceman, S. 2021. Unwinding the roles of RNA helicase MOV10. WIREs Wiley Interdisciplinary Reviews. Jul 29:e1682. doi: 10.1002/wrna.1682
Kenny, P.J., Kim, M., Skariah, G., Nielsen, J., Lannom, M.C., and Ceman, S. 2020. The FMRP-MOV10 complex: A translational regulatory switch modulated by G-Quadruplexes. Nucleic Acids Research.
DeThorne, L. and Ceman, S. 2018. Genetic testing and autism: Tutorial for communication sciences and disorders. J. Communication Disorders. 74:61-73
Skariah, G., Perry, K. J., Drnevich, J., Henry, J. J. and Ceman, S. 2017. Mov10 is essential for gastrulation and CNS development. Dev Dyn. 247(4): 660-671. PMID:29266590 • Featured as the cover article 04/2018 • Referenced in a F1000 Faculty review
Skariah, G., Seimetz, J., Norsworthy, M., Lannom, M.C., Kenny, P. J., Elrakhawy, M., Forsthoefel, C., Drnevich, J., Kalsotra, A., Ceman. S. (2017). Mov10 suppresses retroelements and regulates neuronal development and function in developing brain. BMC Biology. 15(1):54 PMID:28662698 • Recommended by Faculty of 1000
Kenny, P. J. and Ceman, S. 2016. RNA secondary structure modulates FMRP’s bi-functional role in the microRNA pathway. International Journal of Molecular Sciences.17(6): pii: E985
Kenny, P.J., Zhou, H., Kim, M., Skariah, G., Khetani, R.S., Drnevich, J., Arcila, M.L., Kosik, K.S., Ceman, S. 2014. MOV10 and FMRP Regulate AGO2 Association with MicroRNA Recognition Elements. Cell Rep. 9(5): 1729-41
Kim, M. and S. Ceman. 2012. Fragile X Mental Retardation Protein: Past, Present and Future. Current Protein & Peptide Science. 13: 358-371
Blackwell, E. and Ceman, S. 2012. Arginine methylation of RNA binding proteins regulates cell function and differentiation. Molecular Reproductive Physiology.79:163-175
Winograd, C. and Ceman, S. 2011. Fragile X family members have important and non-overlapping functions. Biomolecular Concepts. Oct 1;2(5):343-52
Blackwell. E. and Ceman, S. 2011. Novel regulatory function of region proximal to RGG box in Fragile X Mental Retardation Protein. J. Cell Science. 124: 3060-3065.
Ceman, S. and Saugstad, J. 2011. MicroRNAs: Meta-controllers of gene expression in synaptic activity emerge as genetic and diagnostic markers of human disease. Pharmacology and Therapeutics. 130(1): 26-37.
Cheever, A., Blackwell, E., Ceman, S. 2010. Fragile X protein family member FXR1P is regulated by microRNAs. RNA.18 (8): 1530-1539
Blackwell, E. , Zhang, X. and Ceman, S. 2010. Arginines of the RGG box regulate FMRP association with polyribosomes and mRNA. Hum. Mol. Gen.. 19(7): 1314-1323. PMC2838539.
Cheever, A. and Ceman. S. 2009. Phosphorylation of FMRP inhibits association with Dicer. RNA. 15(3): 362-366.
Nawaz, A., Kenny, P. J., Shilikbay, T., Reed, M., Stuchlik, O., Pohl, J., & Ceman, S. (2023). Serine 970 of RNA helicase MOV10 is phosphorylated and controls unfolding activity and fate of mRNAs targeted for AGO2-mediated silencing. Journal of Biological Chemistry, 299(4), Article 104577. https://doi.org/10.1016/j.jbc.2023.104577
Nawaz, A., Shilikbay, T., Skariah, G., & Ceman, S. (2022). Unwinding the roles of RNA helicase MOV10. Wiley Interdisciplinary Reviews: RNA, 13(2), Article e1682. https://doi.org/10.1002/wrna.1682
Lannom, M. C., Nielsen, J., Nawaz, A., Shilikbay, T., & Ceman, S. (2021). FMRP and MOV10 regulate Dicer1 expression and dendrite development. PloS one, 16(11 November), Article e0260005. https://doi.org/10.1371/journal.pone.0260005
Kenny, P. J., Kim, M., Skariah, G., Nielsen, J., Lannom, M. C., & Ceman, S. (2020). The FMRP-MOV10 complex: A translational regulatory switch modulated by G-Quadruplexes. Nucleic acids research, 48(2), 862-878. https://doi.org/10.1093/nar/gkz1092
DeThorne, L. S., & Ceman, S. (2018). Genetic testing and autism: Tutorial for communication sciences and disorders. Journal of Communication Disorders, 74, 61-73. https://doi.org/10.1016/j.jcomdis.2018.05.003