Diverse human extracellular RNAs are widely detected in human plasma.
There is growing appreciation for the importance of non-protein-coding genes in development and disease. Although much is known about microRNAs, limitations in bioinformatic analyses of RNA sequencing have precluded broad assessment of other forms of small-RNAs in humans. By analysing sequencing data from plasma-derived RNA from 40 individuals, here we identified over a thousand human extracellular RNAs including microRNAs, piwi-interacting RNA (piRNA), and small nucleolar RNAs. Using a targeted quantitative PCR with reverse transcription approach in an additional 2,763 individuals, we characterized almost 500 of the most abundant extracellular transcripts including microRNAs, piRNAs and small nucleolar RNAs. The presence in plasma of many non-microRNA small-RNAs was confirmed in an independent cohort. We present comprehensive data to demonstrate the broad and consistent detection of diverse classes of circulating non-cellular small-RNAs from a large population.
University of Massachusetts Medical School, Department of Medicine, Division of Cardiovascular Medicine, Worcester, Massachusetts 01605, USA.
Jane E
JE
Freedman
Yale University Medical School, Computational Biology and Bioinformatics Program, New Haven, Connecticut 06520, USA.
Mark
M
Gerstein
University of Massachusetts Medical School, Department of Quantitative Health Sciences, Worcester, Massachusetts 01605, USA.
Eric
E
Mick
Yale University Medical School, Computational Biology and Bioinformatics Program, New Haven, Connecticut 06520, USA.
Joel
J
Rozowsky
The Framingham Heart Study, Framingham, Massachusetts 01702, USA.|Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20824, USA.
Daniel
D
Levy
Yale University Medical School, Computational Biology and Bioinformatics Program, New Haven, Connecticut 06520, USA.
Robert
R
Kitchen
Cardiovascular Institute, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
Saumya
S
Das
Cardiovascular Institute, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
Ravi
R
Shah
Cardiovascular Institute, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
Kirsty
K
Danielson
University of Massachusetts Medical School, Department of Medicine, Division of Cardiovascular Medicine, Worcester, Massachusetts 01605, USA.
Lea
L
Beaulieu
Yale University Medical School, Computational Biology and Bioinformatics Program, New Haven, Connecticut 06520, USA.
Fabio C P
FC
Navarro
Center for Cancer Computational Biology, Dana Farber Cancer Institute, Boston, Massachusetts 02215, USA.
Yaoyu
Y
Wang
Yale University Medical School, Computational Biology and Bioinformatics Program, New Haven, Connecticut 06520, USA.
Timur R
TR
Galeev
Center for Cancer Computational Biology, Dana Farber Cancer Institute, Boston, Massachusetts 02215, USA.
Alex
A
Holman
Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Raymond Y
RY
Kwong
University of Michigan, Ann Arbor, Michigan 48409, USA.
Venkatesh
http://orcid.org/0000-0002-7901-1321
V
Murthy
University of Massachusetts Medical School, Department of Medicine, Division of Cardiovascular Medicine, Worcester, Massachusetts 01605, USA.
Selim E
SE
Tanriverdi
University of Massachusetts Medical School, Department of Medicine, Division of Cardiovascular Medicine, Worcester, Massachusetts 01605, USA.
Milka
M
Koupenova-Zamor
University of Massachusetts Medical School, Department of Medicine, Division of Cardiovascular Medicine, Worcester, Massachusetts 01605, USA.
Ekaterina
http://orcid.org/0000-0001-6275-4463
E
Mikhalev
University of Massachusetts Medical School, Department of Medicine, Division of Cardiovascular Medicine, Worcester, Massachusetts 01605, USA.
Kahraman
K
Tanriverdi
D000368:Aged; D005260:Female; D005786:Gene Expression Regulation; D015894:Genome, Human; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D058977:Molecular Sequence Annotation; D034741:RNA, Small Interfering / Q000097:blood / Q000235:genetics*; D020537:RNA, Small Nucleolar / Q000097:blood / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D014481:United States
D035683:MicroRNAs; D034741:RNA, Small Interfering; D020537:RNA, Small Nucleolar