A comprehensive profile of circulating RNAs in human serum

Sinan Uğur Umu; Hilde Langseth; Cecilie Bucher-Johannessen; Bastian Fromm; Andreas Keller; Eckart Meese; Marianne Lauritzen; Magnus Leithaug; Robert Lyle; Trine B Rounge

doi:10.1080/15476286.2017.1403003

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.

Authors

Affiliations

¹ a Department of Research , Cancer Registry of Norway , Oslo , Norway.
² b Department of Tumor Biology , Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital , Nydalen, Oslo , Norway.
³ c Department of Clinical Bioinformatics , Saarland University , Saarbruecken , Germany.
⁴ d Department of Human Genetics , Saarland University , Homburg/Saar , Germany.
⁵ e Department of Medical Genetics , Oslo University Hospital and University of Oslo , Oslo , Norway.
⁶ f PharmaTox Strategic Research Initiative, School of Pharmacy, Faculty of Mathematics and Natural Sciences , University of Oslo , Oslo , Norway.

Abstract

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*

Substances

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

Grants and funding

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.