Integrative analyses of RNA editing, alternative splicing, and expression of young genes in human brain transcriptome by deep RNA sequencing

J Mol Cell Biol. 2015 Aug;7(4):314-25. doi: 10.1093/jmcb/mjv043. Epub 2015 Jul 17.

Abstract

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.

Keywords: RNA editing; human brain evolution; human brain transcriptome; young gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing / genetics*
  • Amino Acids / genetics
  • Brain / metabolism*
  • Epistasis, Genetic
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Gene Regulatory Networks
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • Models, Biological
  • Open Reading Frames / genetics
  • RNA Editing / genetics*
  • Sequence Analysis, RNA / methods*
  • Transcriptome / genetics*

Substances

  • Amino Acids