Widespread splicing changes in human brain development and aging.

Pavel Mazin, Jieyi Xiong, Xiling Liu, Zheng Yan, Xiaoyu Zhang, Mingshuang Li, Liu He, Mehmet Somel, Yuan Yuan, Yi-Ping Phoebe Chen, Na Li, Yuhui Hu, Ning Fu, Zhibin Ning, Rong Zeng, Hongyi Yang, Wei Chen, Mikhail Gelfand, Philipp Khaitovich

Index: Mol. Syst. Biol. 9 , 633, (2013)

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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.