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Integrative analyses of RNA editing, alternative splicing, and expression of young genes in human brain transcriptome by deep RNA sequencing Free
Dong-Dong Wu1,2,†, Ling-Qun Ye1,2,3,†, Yan Li1,2,†, Yan-Bo Sun1,2, Yi Shao4, Chunyan Chen4, Zhu Zhu5, Li Zhong5, Lu Wang5, David M. Irwin1,6,7, Yong E. Zhang4, and Ya-Ping Zhang1,2,5,*
1State Key Laboratory of Genetic Resources and Evolution, Yunnan Laboratory of Molecular Biology of Domestic Animals, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China
2Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming 650204, China
3University of Chinese Academy of Sciences, Beijing, China
4Key Laboratory of Zoological Systematics and Evolution, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
5Laboratory for Conservation and Utilization of Bio-resource, Yunnan University, Kunming 650091, China
6Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada
7Banting and Best Diabetes Centre, University of Toronto, Toronto, Canada *Correspondence to:Ya-Ping Zhang, E-mail: zhangyp@mail.kiz.ac.cn
J Mol Cell Biol, Volume 7, Issue 4, August 2015, 314-325,  https://doi.org/10.1093/jmcb/mjv043
Keyword: RNA editing, human brain transcriptome, young gene, human brain evolution

Next-generation RNA sequencing has been successfully used for identification of transcript assembly, evaluation of gene expression levels, and detection of post-transcriptional modifications. Despite these large-scale studies, additional comprehensive RNA-seq data from different subregions of the human brain are required to fully evaluate the evolutionary patterns experienced by the human brain transcriptome. Here, we provide a total of 6.5 billion RNA-seq reads from different subregions of the human brain. A significant correlation was observed between the levels of alternative splicing and RNA editing, which might be explained by a competition between the molecular machineries responsible for the splicing and editing of RNA. Young human protein-coding genes demonstrate biased expression to the neocortical and non-neocortical regions during evolution on the lineage leading to humans. We also found that a significantly greater number of young human protein-coding genes are expressed in the putamen, a tissue that was also observed to have the highest level of RNA-editing activity. The putamen, which previously received little attention, plays an important role in cognitive ability, and our data suggest a potential contribution of the putamen to human evolution.