Diverse human extracellular RNAs are widely detected in human plasma

Jane E. Freedman (), Mark Gerstein, Eric Mick, Joel Rozowsky, Daniel Levy, Robert Kitchen, Saumya Das, Ravi Shah, Kirsty Danielson, Lea Beaulieu, Fabio C. P. Navarro, Yaoyu Wang, Timur R. Galeev, Alex Holman, Raymond Y. Kwong, Venkatesh Murthy, Selim E. Tanriverdi, Milka Koupenova, Ekaterina Mikhalev and Kahraman Tanriverdi
Additional contact information
Jane E. Freedman: University of Massachusetts Medical School
Mark Gerstein: Yale University Medical School, Computational Biology and Bioinformatics Program
Eric Mick: University of Massachusetts Medical School
Joel Rozowsky: Yale University Medical School, Computational Biology and Bioinformatics Program
Daniel Levy: The Framingham Heart Study
Robert Kitchen: Yale University Medical School, Computational Biology and Bioinformatics Program
Saumya Das: Cardiovascular Institute, Beth Israel Deaconess Medical Center
Ravi Shah: Cardiovascular Institute, Beth Israel Deaconess Medical Center
Kirsty Danielson: Cardiovascular Institute, Beth Israel Deaconess Medical Center
Lea Beaulieu: University of Massachusetts Medical School
Fabio C. P. Navarro: Yale University Medical School, Computational Biology and Bioinformatics Program
Yaoyu Wang: Center for Cancer Computational Biology, Dana Farber Cancer Institute
Timur R. Galeev: Yale University Medical School, Computational Biology and Bioinformatics Program
Alex Holman: Center for Cancer Computational Biology, Dana Farber Cancer Institute
Raymond Y. Kwong: Brigham and Women's Hospital
Venkatesh Murthy: University of Michigan
Selim E. Tanriverdi: University of Massachusetts Medical School
Milka Koupenova: University of Massachusetts Medical School
Ekaterina Mikhalev: University of Massachusetts Medical School
Kahraman Tanriverdi: University of Massachusetts Medical School

Nature Communications, 2016, vol. 7, issue 1, 1-14

Abstract: Abstract 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.

Date: 2016
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DOI: 10.1038/ncomms11106

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