title: Widespread splicing changes in human brain development and aging.
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.
authors: Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Chinese Academy of Sciences, Shanghai, China.
authors: Pavel
authors: P
authors: Mazin
authors: Jieyi
authors: J
authors: Xiong
authors: Xiling
authors: X
authors: Liu
authors: Zheng
authors: Z
authors: Yan
authors: Xiaoyu
authors: X
authors: Zhang
authors: Mingshuang
authors: M
authors: Li
authors: Liu
authors: L
authors: He
authors: Mehmet
authors: M
authors: Somel
authors: Yuan
authors: Y
authors: Yuan
authors: Yi-Ping
authors: YP
authors: Phoebe Chen
authors: Na
authors: N
authors: Li
authors: Yuhui
authors: Y
authors: Hu
authors: Ning
authors: N
authors: Fu
authors: Zhibin
authors: Z
authors: Ning
authors: Rong
authors: R
authors: Zeng
authors: Hongyi
authors: H
authors: Yang
authors: Wei
authors: W
authors: Chen
authors: Mikhail
authors: M
authors: Gelfand
authors: Philipp
authors: P
authors: Khaitovich
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D017398:Alternative Splicing; D000818:Animals; D002531:Cerebellum / Q000254:growth & development / Q000502:physiology*; D002648:Child; D002675:Child, Preschool; D005091:Exons; D020869:Gene Expression Profiling; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008253:Macaca mulatta / Q000235:genetics; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000254:growth & development / Q000502:physiology*; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012326:RNA Splicing; D017423:Sequence Analysis, RNA / Q000379:methods; D055815:Young Adult
chemical_list: D011506:Proteins