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Fuzzy thinking: single neuron variation in RNA state space

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A neuron is one of the most complex cells in our body. In particular, its functional units are individual processes (dendrites and axons) with their complement of synapses rather than the whole cell. In the last four years, we have been working with Jim Eberwine (Penn Pharmacology) to investigate the RNA metabolism underlying a neuron’s developmental phenotype and its dendritic function. Using whole transcriptome manipulations, we have demonstrated that cellular phenotypes can be transdifferentiated into other stable types. In particular, we have found that the RNA states underlying cell types is much more variable than previously thought. An important aspect of neuronal function is posttranscriptional regulation of subcellular localization of RNA . Using computational analysis, we found a surprising contribution from a rapidly evolving retroviral element in mediating RNA localization. Using comparative analysis of the dendritic transcriptome, we show high rates of divergence in post-transcriptional subcellular localization between rats and mice. We propose that evolution of neuronal function involves not only neuroanatomy but modulation of individual synaptic responses.

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