Widespread splicing changes in human brain development and aging

被引:149
作者
Mazin, Pavel [1 ,2 ]
Xiong, Jieyi [1 ]
Liu, Xiling [1 ]
Yan, Zheng [1 ]
Zhang, Xiaoyu [1 ,3 ]
Li, Mingshuang [1 ,3 ]
He, Liu [1 ]
Somel, Mehmet [1 ,4 ]
Yuan, Yuan [1 ,5 ]
Chen, Yi-Ping Phoebe [5 ]
Li, Na [6 ]
Hu, Yuhui [6 ]
Fu, Ning [7 ]
Ning, Zhibin [7 ]
Zeng, Rong [7 ]
Yang, Hongyi [3 ]
Chen, Wei [6 ,8 ]
Gelfand, Mikhail [2 ,9 ]
Khaitovich, Philipp [1 ,4 ]
机构
[1] Chinese Acad Sci, Key Lab Computat Biol, CAS MPG Partner Inst Computat Biol, Shanghai 200031, Peoples R China
[2] Moscow MV Lomonosov State Univ, Dept Bioengn & Bioinformat, Moscow, Russia
[3] NE Forestry Univ, Coll Life Sci, Harbin, Peoples R China
[4] Max Planck Inst Evolutionary Anthropol, Leipzig, Germany
[5] La Trobe Univ, Dept Comp Sci & Comp Engn, Melbourne, Vic, Australia
[6] Max Delbruck Ctr Mol Med, Berlin Inst Med Syst Biol, D-13125 Berlin, Germany
[7] Chinese Acad Sci, Key Lab Syst Biol, Shanghai 200031, Peoples R China
[8] Max Planck Inst Mol Genet, D-14195 Berlin, Germany
[9] Inst Informat Transmiss Problems RAS, Moscow, Russia
基金
中国国家自然科学基金;
关键词
alternative splicing; brain; development; human; RNA-seq; SYNAPTIC GLYCOPROTEIN NEUROPLASTIN; HUMAN PREFRONTAL CORTEX; MESSENGER-RNA; TRANSCRIPTOME DATABASE; BINDING-PROTEIN; GENOME; IDENTIFICATION; EXPRESSION; NEURONS; CHIMPANZEES;
D O I
10.1038/msb.2012.67
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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
引用
收藏
页数:14
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