University of Exeter, Exeter, UK.
University of Exeter, Exeter, UK; Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
Cell Rep. 2021 Nov 16;37(7):110022. doi: 10.1016/j.celrep.2021.110022.
Alternative splicing is a post-transcriptional regulatory mechanism producing distinct mRNA molecules from a single pre-mRNA with a prominent role in the development and function of the central nervous system. We used long-read isoform sequencing to generate full-length transcript sequences in the human and mouse cortex. We identify novel transcripts not present in existing genome annotations, including transcripts mapping to putative novel (unannotated) genes and fusion transcripts incorporating exons from multiple genes. Global patterns of transcript diversity are similar between human and mouse cortex, although certain genes are characterized by striking differences between species. We also identify developmental changes in alternative splicing, with differential transcript usage between human fetal and adult cortex. Our data confirm the importance of alternative splicing in the cortex, dramatically increasing transcriptional diversity and representing an important mechanism underpinning gene regulation in the brain. We provide transcript-level data for human and mouse cortex as a resource to the scientific community.
选择性剪接是一种转录后调控机制，它能从单个前体 RNA 产生不同的 mRNA 分子，在中枢神经系统的发育和功能中起着重要作用。我们使用长读长转录本测序技术在人和鼠大脑皮层中生成全长转录本序列。我们鉴定了新的转录本，这些转录本不存在于现有的基因组注释中，包括映射到假定的新（未注释）基因的转录本和包含多个基因外显子的融合转录本。人类和鼠大脑皮层之间的转录本多样性的整体模式相似，但某些基因在物种间存在显著差异。我们还发现了选择性剪接的发育变化，人类胎儿和成人大脑皮层之间的转录本使用存在差异。我们的数据证实了选择性剪接在大脑皮层中的重要性，极大地增加了转录本的多样性，并代表了大脑中基因调控的重要机制。我们为人类和鼠大脑皮层提供了转录本水平的数据，作为科学界的资源。
