Widespread splicing changes in human brain development and aging
Open accessAbstract
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.
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Nine out of ten genes are differentially expressed or spliced across brain regions and/or time.
“Of these, nine out of ten genes were differentially expressed or spliced across brain regions and/or time (Kang et al., 2011; Mazin et al., 2013).”
From The Cellular and Molecular Landscapes of the Developing Human Central Nervous System (2016) · cites this paper as Mazin et al., 2013
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- Authors
- Mazin, P., Xiong, J., Liu, X., Yan, Z., Zhang, X., Li, M., He, L., Somel, M., Yuan, Y., Phoebe Chen, Y., Li, N., Hu, Y., Fu, N., Ning, Z., Zeng, R., Yang, H., Chen, W., Gelfand, M., & Khaitovich, P.
- Affiliations
- Chinese Academy of Sciences (CN)
- La Trobe University (AU)
- Max Delbrück Center (DE)
- Northeast Forestry University (CN)
- Lomonosov Moscow State University (RU)
- Corresponding author
- Chen, Wei
- Gelfand, Mikhail
- Khaitovich, Philipp
- ORCID
- Venue
- Molecular Systems Biology
- Published
- 2013-01-22
- Volume
- 9
- Issue
- 1
- Pages
- 633-633
- ISSN
- 1744-4292 (ISSN-L)
- PMC
- PMC3564255
- OpenAlex
- W2146646792
- Cited by
- 216
- References
- 53
- Citations by year
- 2026: 11 · 2025: 19 · 2024: 14 · 2023: 17 · 2022: 12 · 2021: 14 · 2020: 24 · 2019: 19 · 2018: 11 · 2017: 15 · 2016: 13 · 2015: 17 · 2014: 20 · 2013: 10
- FWCI
- 8.95
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Molecular Systems Biology (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- OpenMETU (Middle East Technical University) (submittedVersion, cc-by-nc-nd)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- National Natural Science Foundation of China
- Chinese Academy of Sciences (KSCX2-EW-R-02, KSCX2-EW-J-15)
- Russian Academy of Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Keywords
- alternative splicing, brain development, brain aging, prefrontal cortex, cerebellum, human lifespan, rhesus monkeys, splicing factors, nonsense-mediated mRNA decay, transcriptome
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Aging, Animals, Cerebellum, Child, Child, Preschool, Exons, Humans, Infant, Infant, Newborn, Macaca mulatta, Middle Aged, Proteins, RNA Splicing, Prefrontal Cortex, Alternative Splicing, Sequence Analysis, RNA, Gene Expression Profiling, Young Adult
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