SRA

Differences in transcript splicing are well documented among tissues and between sexes in humans and other organisms1-4. Further, splicing changes in selected genes have been reported in human and mouse brain development5-6. Here, using high-throughput RNA sequencing, we characterized the transcriptome-wide splicing changes occurring over the lifespan in the human brain. We found that in two brain regions, prefrontal cortex and cerebellum, as many as 37% of all expressed protein-coding multi-exon genes undergo significant splicing changes between birth and 98 years of age. Approximately 40% of these changes take place in aging. We confirmed our findings using exon arrays and PCRs and detected identified splicing changes at the protein level. We further associated distinct patterns of age-related splicing changes with expression of the corresponding splicing factors. Thus, splicing plays an important role in shaping the human brain transcriptome in both development and aging.