生命科学研究2025，Vol.29Issue(5)：441-453,13.DOI:10.16605/j.cnki.1007-7847.2025.03.0132
人类特异性微外显子的鉴定及其在脑疾病中的潜在作用
Identification of Human-specific Microexons and Their Potential Roles in Brain Disorders
摘要
Abstract
Microexons,a special category of exons,are widely present in the genes of animals and humans.They are highly conserved and usually encode motifs that mediate protein interactions.Their alternative splicing plays a role in regulating protein interaction networks.However,it is still unclear whether there are human-specific microexons and whether they participate in brain disorders.By using exon skipping,the most common alternative splicing event,as an entry point,this study conducted a systematic comparison of eight vertebrate genomes and successfully identified 48 human-specific microexons distributed across 40 genes.Searches of the DECIPHER database revealed that 97.5％(39/40)of the genes containing human-spe-cific microexons had copy number variations linked to intellectual disability phenotypes.An analysis of can-didate genes for brain disorders showed that the 40 genes with human-specific microexons were significantly enriched in schizophrenia candidate genes(18/40).Moreover,the motifs encoded by the 48 microexons me-diated 996 protein interactions through binding to protein domains.The genes encoding these interacting proteins were significantly enriched in candidate genes for schizophrenia,autism spectrum disorder,and in-tellectual disability.Further analysis of transcriptome sequencing data showed that over half of the genes containing human-specific microexons were abnormally expressed in the brain tissues of schizophrenia and autism spectrum disorder patients.These findings collectively suggest that human-specific microexons play critical roles in the human brain and that their mutations may be involved in brain disorders.关键词
可变剪接/外显子跳读/微外显子/精神分裂症/孤独症谱系障碍/脑Key words
alternative splicing/exon skipping/microexon/schizophrenia/autism spectrum disorder/brain分类
生物科学引用本文复制引用
邹晓晴,李美玲,杨小雪,杨新平..人类特异性微外显子的鉴定及其在脑疾病中的潜在作用[J].生命科学研究,2025,29(5):441-453,13.基金项目
国家自然科学基金面上项目(82071503) （82071503）
广东省省级科技计划项目(2017B020227010) （2017B020227010）
