Analysis of intronic and exonic reads in RNA-seq data characterizes transcriptional and post-transcriptional regulation

Nat Biotechnol. 2015 Jul;33(7):722-9. doi: 10.1038/nbt.3269. Epub 2015 Jun 22.


RNA-seq experiments generate reads derived not only from mature RNA transcripts but also from pre-mRNA. Here we present a computational approach called exon-intron split analysis (EISA) that measures changes in mature RNA and pre-mRNA reads across different experimental conditions to quantify transcriptional and post-transcriptional regulation of gene expression. We apply EISA to 17 diverse data sets to show that most intronic reads arise from nuclear RNA and changes in intronic read counts accurately predict changes in transcriptional activity. Furthermore, changes in post-transcriptional regulation can be predicted from differences between exonic and intronic changes. EISA reveals both transcriptional and post-transcriptional contributions to expression changes, increasing the amount of information that can be gained from RNA-seq data sets.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Computational Biology
  • Exons / genetics*
  • Gene Expression Profiling
  • Gene Expression Regulation / genetics*
  • Humans
  • Introns / genetics*
  • Mice
  • Organ Specificity
  • RNA* / genetics
  • RNA* / metabolism
  • Sequence Analysis, RNA / methods*
  • Transcription, Genetic / genetics


  • RNA