LINE-1 逆转录转座子驱动人类神经元转录组的复杂性和功能多样化。
LINE-1 retrotransposons drive human neuronal transcriptome complexity and functional diversification.
发表日期:2023 Nov 03
作者:
Raquel Garza, Diahann A M Atacho, Anita Adami, Patricia Gerdes, Meghna Vinod, PingHsun Hsieh, Ofelia Karlsson, Vivien Horvath, Pia A Johansson, Ninoslav Pandiloski, Jon Matas-Fuentes, Annelies Quaegebeur, Antonina Kouli, Yogita Sharma, Marie E Jönsson, Emanuela Monni, Elisabet Englund, Evan E Eichler, Molly Gale Hammell, Roger A Barker, Zaal Kokaia, Christopher H Douse, Johan Jakobsson
来源:
Epigenetics & Chromatin
摘要:
人类大脑尺寸和复杂性扩展的遗传机制仍然知之甚少。长散布的核元件 1 (L1) 反转录转座子是人科动物基因组中不同遗传信息的来源,但它们在生理功能中的重要性及其对人类大脑进化的贡献在很大程度上尚不清楚。通过多组学分析,我们证明 L1 启动子在发育中和成人大脑中动态活跃。 L1 产生数百个发育调节和细胞类型特异性转录本,其中许多被选为嵌合转录本或调节 RNA。 L1 衍生的长非编码 RNA LINC01876 是一种在大脑发育过程中专门表达的人类特异性转录本。 LINC01876 的 CRISPR 干扰沉默导致大脑类器官尺寸减小和神经祖细胞过早分化,这表明 L1 与人类特异性发育过程有关。总之,我们的结果表明,L1 衍生的转录本提供了先前未描述的灵长类和人类特异性转录组复杂性,有助于人脑的功能多样化。
The genetic mechanisms underlying the expansion in size and complexity of the human brain remain poorly understood. Long interspersed nuclear element-1 (L1) retrotransposons are a source of divergent genetic information in hominoid genomes, but their importance in physiological functions and their contribution to human brain evolution are largely unknown. Using multiomics profiling, we here demonstrate that L1 promoters are dynamically active in the developing and the adult human brain. L1s generate hundreds of developmentally regulated and cell type-specific transcripts, many that are co-opted as chimeric transcripts or regulatory RNAs. One L1-derived long noncoding RNA, LINC01876, is a human-specific transcript expressed exclusively during brain development. CRISPR interference silencing of LINC01876 results in reduced size of cerebral organoids and premature differentiation of neural progenitors, implicating L1s in human-specific developmental processes. In summary, our results demonstrate that L1-derived transcripts provide a previously undescribed layer of primate- and human-specific transcriptome complexity that contributes to the functional diversification of the human brain.