Recurrent chimeric fusion RNAs in non-cancer tissues and cells

Nucleic Acids Res. 2016 Apr 7;44(6):2859-72. doi: 10.1093/nar/gkw032. Epub 2016 Feb 2.


Gene fusions and their products (RNA and protein) were once thought to be unique features to cancer. However, chimeric RNAs can also be found in normal cells. Here, we performed, curated and analyzed nearly 300 RNA-Seq libraries covering 30 different non-neoplastic human tissues and cells as well as 15 mouse tissues. A large number of fusion transcripts were found. Most fusions were detected only once, while 291 were seen in more than one sample. We focused on the recurrent fusions and performed RNA and protein level validations on a subset. We characterized these fusions based on various features of the fusions, and their parental genes. They tend to be expressed at higher levels relative to their parental genes than the non-recurrent ones. Over half of the recurrent fusions involve neighboring genes transcribing in the same direction. A few sequence motifs were found enriched close to the fusion junction sites. We performed functional analyses on a few widely expressed fusions, and found that silencing them resulted in dramatic reduction in normal cell growth and/or motility. Most chimeras use canonical splicing sites, thus are likely products of 'intergenic splicing'. We also explored the implications of these non-pathological fusions in cancer and in evolution.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / cytology
  • Astrocytes / metabolism
  • Base Sequence
  • Cell Line, Transformed
  • Computational Biology
  • Evolution, Molecular
  • Fibroblasts / cytology
  • Fibroblasts / metabolism*
  • Gene Fusion*
  • Gene Library
  • Gene Silencing
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism*
  • Mice
  • Molecular Sequence Data
  • Primary Cell Culture
  • RNA Splicing*
  • RNA, Messenger / antagonists & inhibitors
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Sequence Analysis, RNA
  • Species Specificity


  • RNA, Messenger
  • RNA, Small Interfering