Molecular basis of disease, post-translational modifications, regulation of RNA expression, RNA-protein interactions, microRNAs
Our goal is to gain insight into the molecular basis of learning and memory by using the fragile X mental retardation protein, FMRP, as a model system. Fragile X syndrome is one of the most common forms of inherited mental retardation, with an incidence of 1 in 4000 live male births and 1 in 8000 female births. Patients with fragile X syndrome are not able to express the protein FMRP (fragile X mental retardation protein), which is one of a growing number of proteins involved in normal cognitive function. Although much is known about FMRP—it is an RNA binding protein that shuttles into and out of the nucleus and associates with actively translating polyribosomes—it is still unclear how all of these functions are regulated. Our goal is to understand how the activities of FMRP are modulated, both at the protein and RNA level, and how genetic alterations in this process may lead to instructive phenotypes.
We are interested in how FMRP uses microRNAs and microRNA pathway proteins to regulate translation of its bound mRNAs. We are particularly interested in how FMRP functions with the helicase MOV10 to regulate translation.
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Kenny, P.J., Zhou, H., Kim, M., Skariah, G., Khetani, R. S., Drnevich, J., Luz Arcila, M., Kosik, K.S., Ceman, S. 2014. MOV10 and FMRP regulate AGO2 association with microRNA recognition elements. Cell Reports. 9(5): 1729-41 PMID: 25464849
Kim, M. and S. Ceman. 2012. Fragile X Mental Retardation Protein: Past, Present and Future. Current Protein & Peptide Science (CPPS). 13(4):358-71
Blackwell, E. and Ceman, S. 2012. Arginine methylation of RNA binding proteins regulates cell function and differentiation. Molecular Reproduction and Development. 79(3):163-175.
Winograd, C. and Ceman, S. 2012. Fragile X family members have important and non-overlapping functions. Biomolecular Concepts.
Winograd, C. and Ceman, S. 2012. Exploring the zebra finch as a novel animal model for the speech-language deficit in Fragile X syndrome. Results Prob.Cell Differ. 54: 181-197. PMID: 22009353
Blackwell. E. and Ceman, S. 2011. A new regulatory function of the region proximal to RGG box in Fragile X Mental Retardation Protein. J. Cell Science. 124: 3060-3065. PMID: 21868366
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.
Cheever, A., Blackwell, Ceman, S. 2010. Fragile X protein family member FXR1P is regulated by microRNAs. RNA. 16(8):1530-9.
Blackwell, E., Zhang, X., Ceman, S. 2010. Arginines of the RGG box regulate FMRP association with polyribosomes and mRNA. Hum. Mol. Gen. 19(7): 1314-1323.
Cheever, A. and Ceman. S. 2009. Translation regulation of mRNAs by the fragile X family of proteins through the microRNA pathway. RNA Biology. 6 (2): 175-178.
Cheever, A. and Ceman. S. 2009. Phosphorylation of FMRP inhibits association with Dicer. RNA. 15(3): 362-366.
Kim, M., Bellini, M., Ceman, S. 2009. Fragile X mental retardation protein FMRP binds mRNAs in the nucleus. MCB. 29(1): 214-228.
Winograd, C., Clayton, D. Ceman, S. 2008. Expression of fragile X mental retardation protein within the vocal control system of developing and adult male zebra finches. Neurosci. 157(1):132-142.
Narayanan, U., Nalavadi, V., Nakamoto, M., Thomas, G., Ceman, S., Bassell, G. J., Warren, S. T. 2008. S6K1 phosphorylates and regulates FMRP with the neuronal protein synthesis-dependent mTOR signaling cascade. J. Biol. Chem. 283(27):18478-82.
Narayanan, U., Nalavadi, V., Nakamoto, M., Pallas, D., Ceman, S., Bassell, G. J., and Warren, S.T. 2007. FMRP phosphorylation reveals an immediate-early signaling pathway triggered by groupI mGluR and mediated by PP2A. J. Neurosci., 27(52):14349-57.
Stetler, A. Winograd, C., Sayegh, J., Cheever, A., Patton, E., Zhang, X., Clarke, S., and Ceman, S. 2006. Identification and characterization of the methyl arginines in the fragile X mental retardation protein Fmrp. Hum. Mol. Genet., 15(1):87-96.
Jin, P., Zarnescu, D.C., Ceman, S., Nakamoto, M., Mowrey, J., Jongens, T.A., Nelson, D.L., Moses, K., and Warren, S.T. 2004. Biochemical and genetic interaction between the fragile X mental retardation protein and the microRNA pathway. Nat. Neurosci., 7(2):113-7
Ceman, S., O‘Donnell, W.T., Reed, M., Patton, S., Pohl, J., and Warren, S.T. (2003) "Phosphorylation regulates translation state of FMRP-associated polyribosomes," Submitted.
Jin, P., Ceman, S., Zarnescu, D., Nakamoto, M., Mowrey, J., Jongens, T.A., Nelson, D., Moses, K., and Warren, S.T. (2003) "Biochemical and genetic interaction between the fragile X mental retardation protein and the microRNA pathway," Submitted.
Coffee, B., Zhang, F., Ceman, S., Warren, S.T., and Reines, D. (2002) "Histone modifications depict an aberrantly heterochromatinized FMR1 gene in fragile X syndrome," Am. J. Hum. Gen. 71:923-32.
Brown, V., Jin, P., Ceman, S., Darnell, J.C., O&lsquoDonnell, W.T., Tenenbaum, S.A., Jin, X., Feng, Y., Wilkinson, K.D., Keene, J.D., Darnell, R.B., and Warren, S.T. (2001) "Microarray identification of FMRP-associated brain mRNAs and altered mRNA translational profiles in fragile X syndrome," Cell 107:477-487.
Ceman, S., Brown, V., and Warren, S.T. (1999) "Isolation of an FMRP-associated messenger ribonucleoprotein particle and identification of nucleolin and the fragile X-related proteins as components of the complex," Mol. Cell Biol. 19:7925-7932.
Ceman, S., Wu, S., Jardetzky, T.S., and Sant, A.J. (1998) "Alteration of a single hydrogen bond between class II molecules and peptide results in rapid degradation of class II molecules after invariant chain removal," J. Exp. Med. 188(11):2139-2149.