神经发育障碍威胁儿童健康。研究发现，神经发育障碍与HNRNPU基因突变高度关联，但分子机制还知之甚少。HNRNPU是核不均一核糖核蛋白成员之一或核基质蛋白A，参与了转录和非编码RNA定位等多个方面的调控。我们初步研究发现，在染色质上HNRNPU选择性结合神经系统发育相关基因。我们认为，HNRNPU调控该类基因表达可能是其在神经发育障碍发生中的分子机制。我们前期的研究发现，HNRNPU广泛结合各种非编码RNA。我们推测，HNRNPU可能通过构建非编码RNA与染色质互作网络来维持神经系统发育相关基因的正常表达。根据该假说，本项目将调查HNRNPU对神经系统发育相关基因的表达调控功能，并运用新技术GRID-seq和GRO-seq，系统研究HNRNPU介导的非编码RNA与神经系统发育相关基因的互作网络和基因表达调控机制。项目研究结果可为神经发育障碍发生提供分子机理，并为其诊疗提供必要的理论依据。

Neurodevelopmental disorders are one of the key threats to child health. Continuous genome-wide association studies (GWAS) found HNRNPU gene mutation is highly associated with neurodevelopmental disorders, however, the molecular mechanism is largely unknown. HNRNPU was characterized as a component of heterogeneous nuclear ribonucleoprotein (RNP) particles or as a nuclear scaffold attachment factor A (SAF-A). HNRNPU has been implicated in diverse pathways, including transcription regulation and non-coding RNA localization. Our preliminary data indicated HNRNPU preferentially associates with genes in the function of nervous system development on chromatin. We hypothesize that the regulation of neurodevelopmental gene expression by HNRNPU may be the mechanism of neurodevelopmental disorders. Additionally, our early investigation on the RNA interactome of HNRNPU found that HNRNPU directly binds diverse classes of non-coding RNAs. Mechanistically, we hypothesize that HNRNPU may build an interaction network between non-coding RNAs and chromatin and maintain the gene expression for neurodevelopment. Based on this hypothesis, we will study the function of HNRNPU in neurodevelopmental gene expression, and employ new techniques, GRID-seq (capture in situ Global RNA Interaction with DNA by deep sequencing) and GRO-seq (Global nuclear Run-On sequencing) to investigate HNRNPU-mediated global interaction network between non-coding RNAs and neurodevelopmental genes as well as the mechanism of gene expression regulation. The results obtained may give us new insights into the molecular mechanism of neurodevelopmental disorders and provide theoretical basis for the diagnosis and therapeutics of the disease.