GSE110727
Characterization of the nuclear and cytosolic transcriptomes in human brain tissue
Transcriptome analysis has mainly relied on analyzing RNA sequencing data from whole cells, overlooking the impact of subcellular RNA localization and its influence on our understanding of gene function, gene expression regulation, and interpretation of gene expression patterns in cells and tissues. Several studies reported significant differences between the cytosol and nuclear transcriptomes and that many coding and non-coding transcripts were unique to either of the compartments. However, these studies is based on cell lines and in most of the cases restricted to target gene experiments. Here, we performed a comprehensive analysis of cytosolic and nuclear transcriptomes in human fetal and adult brain samples. We show significant differences in RNA expression for protein-coding and lncRNA genes between cytosol and nucleus. Transcripts displaying differential subcellular localization belong to particular functional categories and display tissue-specific localization patterns. We also show that transcripts encoding the nuclear-encoded mitochondrial proteins are significantly enriched in the cytosol compared to the rest of protein-coding genes. Further investigation of the reliability of using the cytosol or the nucleus for differential gene expression analysis in single cell experiments as a proxy for whole transcriptome indicates important differences in results depending on the cellular compartment. These differences were manifested at the level of transcript category and number of differentially expressed genes. Our data provides the first resource of RNA subcellular localization of RNA in human brain and highlight the influence of using the cytosol and the nucleus in interpreting and comparing results from single cell studies. Overall design: Nuclear and cytoplasmic fraction of tissues from adult and fetal human frontal cortex and cerebellum.