Characterizing the nuclear and cytoplasmic transcriptomes in developing and mature human cortex uncovers new insight into psychiatric disease gene regulation

• DOI: 10.1101/gr.250217.119
• Publication Date: 2019-12-18T23:55:14Z
• Authors: Amanda J. Price; Taeyoung Hwang; Ran Tao; Emily E. Burke; Anandita Rajpurohit; Joo Heon Shin; Thomas M. Hyde; Joel E. Kleinman; Andrew E. Jaffe; Daniel R. Weinberger
• Keywords: Nuclear gene; Compartmentalization (fire protection)

Transcriptome compartmentalization by the nuclear membrane provides both stochastic and functional buffering of transcript activity in cytoplasm, has recently been implicated neurodegenerative disease processes. Although many mechanisms regulating are also prevalent brain development, extent to which subcellular localization differs as matures yet be addressed. To characterize cytoplasmic transcriptomes during we sequenced RNA fractions from homogenate prenatal adult human postmortem cortex using poly(A)+ Ribo-Zero library preparation methods. We find that while genes differentially expressed fraction developmental expression changes similarly detectable RNA, compartmented become more distinct matures, perhaps reflecting increased utilization retention a regulatory strategy brain. examined potential this divergence including alternative splicing, editing, pore composition, RNA-binding protein motif enrichment, secondary structure. Intron is associated with greater abundance subset transcripts, enrichment for several splicing factor binding motifs. Finally, association fraction-regulated gene sets found nuclear-enriched were preferentially enriched neurodevelopmental psychiatric disorders. These results suggest although gene-level globally comparable between fractions, transcripts may play an underappreciated role regulation brain, particularly whose dysregulation related neuropsychiatric