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RNA. 2018 Apr;24(4):585-596. doi: 10.1261/rna.064931.117. Epub 2018 Jan 23.

Conservation, evolution, and regulation of splicing during prefrontal cortex development in humans, chimpanzees, and macaques.

Mazin PV1,2,3, Jiang X4, Fu N1, Han D4, Guo M4,5,6, Gelfand MS1,2,3,7, Khaitovich P1,4,6,8.

Author information

1
Center for Data-Intensive Biomedicine and Biotechnology, Skolkovo Institute of Science and Technology, Moscow 143028, Russia.
2
Institute for Information Transmission Problems (Kharkevich Institute), Russian Academy of Sciences, Moscow 127051, Russia.
3
Faculty of Computer Science, Higher School of Economics, Moscow 125319, Russia.
4
CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai 200031, China.
5
University of Chinese Academy of Sciences, Beijing 100049, China.
6
School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.
7
Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow 119992, Russia.
8
Max Planck Institute for Evolutionary Anthropology, Leipzig 04103, Germany.

Abstract

Changes in splicing are known to affect the function and regulation of genes. We analyzed splicing events that take place during the postnatal development of the prefrontal cortex in humans, chimpanzees, and rhesus macaques based on data obtained from 168 individuals. Our study revealed that among the 38,822 quantified alternative exons, 15% are differentially spliced among species, and more than 6% splice differently at different ages. Mutations in splicing acceptor and/or donor sites might explain more than 14% of all splicing differences among species and up to 64% of high-amplitude differences. A reconstructed trans-regulatory network containing 21 RNA-binding proteins explains a further 4% of splicing variations within species. While most age-dependent splicing patterns are conserved among the three species, developmental changes in intron retention are substantially more pronounced in humans.

KEYWORDS:

RNA-seq; alternative splicing; brain development; transcriptomics

PMID:
29363555
PMCID:
PMC5855957
DOI:
10.1261/rna.064931.117
[Indexed for MEDLINE]
Free PMC Article

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