A comprehensive profile of circulating RNAs in human serum

RNA Biol. 2018 Feb 1;15(2):242-250. doi: 10.1080/15476286.2017.1403003. Epub 2017 Dec 8.


Non-coding RNA (ncRNA) molecules have fundamental roles in cells and many are also stable in body fluids as extracellular RNAs. In this study, we used RNA sequencing (RNA-seq) to investigate the profile of small non-coding RNA (sncRNA) in human serum. We analyzed 10 billion Illumina reads from 477 serum samples, included in the Norwegian population-based Janus Serum Bank (JSB). We found that the core serum RNA repertoire includes 258 micro RNAs (miRNA), 441 piwi-interacting RNAs (piRNA), 411 transfer RNAs (tRNA), 24 small nucleolar RNAs (snoRNA), 125 small nuclear RNAs (snRNA) and 123 miscellaneous RNAs (misc-RNA). We also investigated biological and technical variation in expression, and the results suggest that many RNA molecules identified in serum contain signs of biological variation. They are therefore unlikely to be random degradation by-products. In addition, the presence of specific fragments of tRNA, snoRNA, Vault RNA and Y_RNA indicates protection from degradation. Our results suggest that many circulating RNAs in serum can be potential biomarkers.

Keywords: Bioinformatics; RNA fragments; Small RNA; cancer; circulating RNA; rna sequencing; serum.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / blood
  • Biomarkers / chemistry
  • Cell-Free Nucleic Acids / blood*
  • Cell-Free Nucleic Acids / chemistry
  • Gene Expression Regulation
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • MicroRNAs / blood
  • MicroRNAs / chemistry
  • RNA Stability
  • RNA, Small Interfering / blood
  • RNA, Small Interfering / chemistry
  • RNA, Small Nucleolar / blood
  • RNA, Small Nucleolar / chemistry
  • RNA, Small Untranslated / blood
  • RNA, Small Untranslated / chemistry
  • RNA, Transfer / blood
  • RNA, Transfer / chemistry
  • Sequence Analysis, RNA / methods*


  • Biomarkers
  • Cell-Free Nucleic Acids
  • MicroRNAs
  • RNA, Small Interfering
  • RNA, Small Nucleolar
  • RNA, Small Untranslated
  • RNA, Transfer

Grant support

The study was funded by the Research Council of Norway under the Program Human Biobanks and Health Data (grant numbers 229621/H10 and 248791/H10). BF was supported by the South-Eastern Norway Regional Health Authority, project number: 229621.