Next-generation sequencing identifies mRNAs targets that experience significant changes in alternative splicing upon PQBP1 knockdown in mouse embryonic cortical neurons. Mus musculus

PQBP1 is a highly conserved protein closely related to neurodegenerative disorders. We identified PQBP1 as an important alternative splicing effector necessary for maintaining normal neuron functions in the brain. In order to explore PQBP1's functions in alternative splicing regulation and neuronal activities, we systematically profiled the alternative splicing targets of PQBP1 in mouse embryonic cortical neurons by RNA-seq. The mRNAs whose alternative splicing are affected by PQBP1 showed tissue-specific functional enrichment especially in neurite outgrowth, with strong Gene Ontology (GO) enrichments for neuron projection development/morphogenesis, dendrite development and axonogenesis. PQBP1's alternative splicing targets are also functionally enriched in RNA splicing, chromatin modification, and ARF signal transduction. Overall design: We applied RNA-seq to compare the transcriptomes of mock and PQBP1 knockdown mouse embryonic cortical neuron samples.

多聚谷氨酰胺结合蛋白1（PQBP1）是一种高度保守的蛋白质，与神经退行性疾病密切相关。本研究鉴定出PQBP1是维持大脑神经元正常功能所必需的重要可变剪接效应因子。为探究PQBP1在可变剪接调控及神经元活动中的功能，本研究通过RNA测序（RNA-seq）系统分析了小鼠胚胎皮层神经元中PQBP1的可变剪接靶标。可变剪接受PQBP1调控的mRNA呈现组织特异性功能富集特征，尤其在神经突生长通路中；基因本体（Gene Ontology，GO）富集分析结果显示，这些靶标显著富集于神经元投射发育/形态发生、树突发育及轴突发生等生物学过程。PQBP1的可变剪接靶标同时在RNA剪接、染色质修饰及ARF信号转导通路中存在功能富集。实验设计概述：本研究通过RNA-seq对比了空白对照与PQBP1敲低的小鼠胚胎皮层神经元样本的转录组。