Nuclear RNA in the nervous system

Background: Recent characterization of the transcriptional landscape of cell lines and whole tissues has suggested widespread transcription of the genome, including loci that produce regulatory non-coding RNAs that function within the nucleus. Methods: Here, we have defined the nuclear transcriptional landscape of the three major cellular divisions of the nervous system using flow sorting of genetically labeled nuclei from bacTRAP mouse lines followed by characterization the unique expression of coding, non-coding and intergenic RNAs in the mature mouse brain with RNAseq, and validation with independent methods. Results: Our findings reveal diverse expression across the cell-types of all classes of RNAs, including long non-coding RNAs - several of which were confirmed as highly enriched in the nuclei of specific cell-types using anatomical methods. Finally, we also discovered several examples of cell-type specific expression of tandem gene fusions, and report the first cell-type specific expression of circular RNAs, notably a neuron specific and nuclear enriched RNA arising from the gene Hnrnpu. Conclusion: These non-coding RNA expression data should provide an important context for studies evaluating the function of a variety of ncRNA in the nervous system. Overall design: Three to four independent replicate samples (each from one mouse) were collected for each of three sample types: Neuronal nuclear RNA, Astrocyte nuclear RNA, Oligodendrocyte nuclear RNA. Controls include low-coverage presorted nuclear RNA from each mouse.

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Reddy AS, O'Brien D, Pisat N, Weichselbaum CT, Sakers K, Lisci M, Dalal JS, Dougherty JD