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Widespread splicing changes in human brain development and aging

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Official URL:https://doi.org/10.1038/msb.2012.67
PubMed:View item in PubMed
Creators Name:Mazin, P. and Xiong, J. and Liu, X. and Yan, Z. and Zhang, X. and Li, M. and He, L. and Somel, M. and Yuan, Y. and Chen, Y.P.P. and Li, N. and Hu, Y. and Fu, N. and Ning, Z. and Zeng, R. and Yang, H. and Chen, W. and Gelfand, M. and Khaitovich, P.
Journal Title:Molecular Systems Biology
Journal Abbreviation:Mol Syst Biol
Volume:9
Page Range:633
Date:2013
Keywords:Alternative Splicing, Brain, Development, Human, RNA-Seq, Animals
Abstract: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.
ISSN:1744-4292
Publisher:Nature Publishing Group (U.K.)
Item Type:Article

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