The long-term goal of this research project is to understand how differentially-expressed trans-acting factors in neurons can control pre-mRNA processing to precisely regulate neuronal gene expression. The powerful genetics, molecular biology and transgenic techniques of Drosophila, along with the emergent DNA microarray technology, will be utilized to study the role of ELAV in mRNA processing and its overall impact on gene expression in neurons. ELAV is the founding member of the ELAV/Hu family of RNA-binding proteins, which is conserved in both vertebrates and invertebrates. Members of the ELAV/Hu family serve diverse roles in mRNA processing, including splicing, stability and translatability.
The aims of the project are: (1) elucidation of mechanisms of ELAV's interactions with RNA transcripts, (2) identification of direct targets of ELAV using immunoprecipitated ELAV-ribnucleoprotein complexes and DNA microarrays, (3) assessment of the overall impact of ELAV on gene expression using microarray technology. Together, these approaches will begin to identify networks of genes that are regulated collectively and provide a comprehensive view of how post-transcriptional regulation is utilized in neuronal gene expression. Given the evolutionary conservation between Drosophila and human genomes, insights in regulatory strategies will be directly transferable to human studies. Human members of the ELAV/Hu family have been implicated in pathogenesis of paraneoplastic cerebellar dysfunction. RNA processing defects have been documented in a large number of human diseases and inherited disorders including cancer, muscular dystrophy and fragile X syndrome.
| Hadži?, Tarik; Park, Dongkook; Abruzzi, Katharine C et al. (2015) Genome-wide features of neuroendocrine regulation in Drosophila by the basic helix-loop-helix transcription factor DIMMED. Nucleic Acids Res 43:2199-215 |
| Guo, Fang; Cerullo, Isadora; Chen, Xiao et al. (2014) PDF neuron firing phase-shifts key circadian activity neurons in Drosophila. Elife 3: |
| Li, Yue; Guo, Fang; Shen, James et al. (2014) PDF and cAMP enhance PER stability in Drosophila clock neurons. Proc Natl Acad Sci U S A 111:E1284-90 |
| Perrat, Paola N; DasGupta, Shamik; Wang, Jie et al. (2013) Transposition-driven genomic heterogeneity in the Drosophila brain. Science 340:91-5 |
| Rinberg, Anatoly; Taylor, Adam L; Marder, Eve (2013) The effects of temperature on the stability of a neuronal oscillator. PLoS Comput Biol 9:e1002857 |
| Li, Yue; Rosbash, Michael (2013) Accelerated degradation of perS protein provides insight into light-mediated phase shifting. J Biol Rhythms 28:171-82 |
| Ni, Lina; Bronk, Peter; Chang, Elaine C et al. (2013) A gustatory receptor paralogue controls rapid warmth avoidance in Drosophila. Nature 500:580-4 |
| Shang, Yuhua; Donelson, Nathan C; Vecsey, Christopher G et al. (2013) Short neuropeptide F is a sleep-promoting inhibitory modulator. Neuron 80:171-83 |
| Luo, Weifei; Li, Yue; Tang, Chih-Hang Anthony et al. (2012) CLOCK deubiquitylation by USP8 inhibits CLK/CYC transcription in Drosophila. Genes Dev 26:2536-49 |
| Tang, Lamont S; Taylor, Adam L; Rinberg, Anatoly et al. (2012) Robustness of a rhythmic circuit to short- and long-term temperature changes. J Neurosci 32:10075-85 |
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