Open AccessWidespread splicing changes in human brain development and aging
Author(s) -
Mazin Pavel,
Xiong Jieyi,
Liu Xiling,
Yan Zheng,
Zhang Xiaoyu,
Li Mingshuang,
He Liu,
Somel Mehmet,
Yuan Yuan,
Phoebe Chen YiPing,
Li Na,
Hu Yuhui,
Fu Ning,
Ning Zhibin,
Zeng Rong,
Yang Hongyi,
Chen Wei,
Gelfand Mikhail,
Khaitovich Philipp
Publication year - 2013
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.1038/msb.2012.67
Subject(s) - rna splicing , biology , alternative splicing , exon , transcriptome , nonsense mediated decay , human brain , aging brain , gene , genetics , rna seq , sr protein , splicing factor , gene expression , rna , neuroscience , cognition
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.