Widespread splicing changes in human brain development and aging
Widespread splicing changes in human brain development and aging
复制标题
人类大脑发育和衰老过程中广泛的剪接变化
DOI：
10.1038/msb.2012.67
复制
发表时间：
2013-01-01
影响因子：
9.9
通讯作者：
Khaitovich, Philipp
中科院分区：
文献类型：
--
作者：
Mazin, Pavel;Xiong, Jieyi;Khaitovich, Philipp
虽然组织、性别和物种之间的剪接差异已被充分记录，但在人类或哺乳动物的发育和衰老过程中，剪接变化的程度和性质却鲜为人知。在这里，使用高通量转录组测序，我们已经表征了剪接变化发生在整个人类生命中的两个大脑区域：前额叶皮层和小脑。使用独立的人类和恒河猴RNA-seq数据集、外显子阵列和PCR确认鉴定的变化，并使用质谱法在蛋白质水平上检测。在研究的两个大脑区域中，剪接的变化在整个生命周期中都很丰富，影响了人类大脑中三分之一以上的基因表达。大约15%的变化在两个大脑区域之间是不同的。在整个生命周期中，剪接变化遵循与神经功能相关的离散模式，并与相应剪接因子的表达谱相关。超过60%的剪接变化代表了单一剪接模式，反映了基因片段的优先包含，可能针对婴儿和老年人中无义介导的衰退的转录本。分子系统生物学9:633；2013年1月22日在线发布；doi: 10.1038 / msb.2012.67
While splicing differences between tissues, sexes and species are well documented, little is known about the extent and the nature of splicing changes that take place during human or mammalian development and aging. Here, using high-throughput transcriptome sequencing, we have characterized splicing changes that take place during whole human lifespan in two brain regions: prefrontal cortex and cerebellum. Identified changes were confirmed using independent human and rhesus macaque RNA-seq data sets, exon arrays and PCR, and were detected at the protein level using mass spectrometry. Splicing changes across lifespan were abundant in both of the brain regions studied, affecting more than a third of the genes expressed in the human brain. Approximately 15% of these changes differed between the two brain regions. Across lifespan, splicing changes followed discrete patterns that could be linked to neural functions, and associated with the expression profiles of the corresponding splicing factors. More than 60% of all splicing changes represented a single splicing pattern reflecting preferential inclusion of gene segments potentially targeting transcripts for nonsense-mediated decay in infants and elderly. Molecular Systems Biology 9: 633; published online 22 January 2013; doi:10.1038/msb.2012.67