Noncoding RNAs are known to regulate gene expression at many levels via a variety of mechanisms. I have a long-term interest in studying the roles of noncoding RNAs in human neurological disorders. In my earlier work, we provided the first link between the miRNA pathway and a genetic disorder, fragile X syndrome.
I also developed a fruit fly model of fragile X-associated tremor/ataxia syndrome and provided the first evidence that RNA itself is sufficient to cause neurodegeneration. Over the last fifteen years, I have continued to study the molecular mechanisms of RNA-mediated neurodegeneration and develop potential therapeutics using both fly and mouse models.
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are heterogeneous illnesses that share a number of clinical, pathologic, and genetic features. Recently, an expanded GGGGCC (G4C2) repeat in C9ORF72 was discovered to be the most common genetic cause of ALS and FTD. We developed a Drosophila model to show that the expanded rG4C2 repeat is sufficient to cause neurodegeneration.
Jin, P., Zarnescu, D.C., Zhang, F., Pearson, C.E., Lucchesi, J.C., Moses, K and Warren, S.T. (2003). RNA-mediated neurodegeneration caused by the fragile X premutation rCGG repeats in Drosophila. Neuron, 39, 739-747. (PMID: 12948442)
Sofola, O.A.*, Jin, P.* (equal contribution), Qin, Y., Duan, R., Liu, H., de Haro, M., Nelson, D.L., and Botas, J. (2007). RNA binding proteins hnRNP A2/B1 and CUGBP1 suppress Fragile X CGG premutation repeat-induced neurodegeneration in a Drosophila model of FXTAS. Neuron, 16, 565-571. PMC2215388
Jin, P.*, Duan, R., Qurashi, A., Qin, Y., Tian, D., Rosser, T.C., Liu, H., Feng, Y., and Warren, S.T.* (2007). Pur a binds to rCGG repeats and modulates repeat-mediated neurodegeneration in a Drosophila model of Fragile X Tremor/Ataxia Syndrome. Neuron, 16, 556-564. (*:Co-Corresponding authors) PMC1994817
Xu, Z., Poidevin, M., Li, X., Li, Y., Shu, L., Nelson, D.L., Li, H., Gearing, M., Wingo, T.S., and Jin, P. (2013) Expanded Hexanucleotide GGGGCC Repeat RNA Associated with ALS/FTD Causes Neurodegeneration. Proceedings of the National Academy of Sciences, 110: 7778-7783. PMC3651485