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, Kahraman Tanriverdi

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.