Pollen-derived RNAs Are Found in the Human Circulation
Milka Koupenova,
Eric Mick,
Heather A. Corkrey,
Anupama Singh,
Selim E. Tanriverdi,
Olga Vitseva,
Daniel Levy,
Allison M. Keeler,
Marzieh Ezzaty Mirhashemi,
Mai K. ElMallah,
Mark Gerstein,
Joel Rozowsky,
Kahraman Tanriverdi,
Jane E. Freedman
Affiliations
Milka Koupenova
Department of Medicine, Division of Cardiovascular Medicine, University of Massachusetts Medical School, 368 Plantation St., AS7-1051, Worcester, MA 01605, USA; Corresponding author
Eric Mick
Department of Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, MA 01605, USA
Heather A. Corkrey
Department of Medicine, Division of Cardiovascular Medicine, University of Massachusetts Medical School, 368 Plantation St., AS7-1051, Worcester, MA 01605, USA
Anupama Singh
Department of Medicine, Division of Cardiovascular Medicine, University of Massachusetts Medical School, 368 Plantation St., AS7-1051, Worcester, MA 01605, USA
Selim E. Tanriverdi
Department of Medicine, Division of Cardiovascular Medicine, University of Massachusetts Medical School, 368 Plantation St., AS7-1051, Worcester, MA 01605, USA
Olga Vitseva
Department of Medicine, Division of Cardiovascular Medicine, University of Massachusetts Medical School, 368 Plantation St., AS7-1051, Worcester, MA 01605, USA
Daniel Levy
The Framingham Heart Study, Framingham, MA, USA; Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
Allison M. Keeler
Department of Pediatrics, Division of Pulmonary Medicine and Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA 01605, USA
Marzieh Ezzaty Mirhashemi
Department of Medicine, Division of Cardiovascular Medicine, University of Massachusetts Medical School, 368 Plantation St., AS7-1051, Worcester, MA 01605, USA
Mai K. ElMallah
Department of Pediatrics, Division of Pulmonary Medicine and Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA 01605, USA
Mark Gerstein
Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA; Department of Computer Science, Yale University, New Haven, CT 06520, USA
Joel Rozowsky
Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA
Kahraman Tanriverdi
Department of Medicine, Division of Cardiovascular Medicine, University of Massachusetts Medical School, 368 Plantation St., AS7-1051, Worcester, MA 01605, USA
Jane E. Freedman
Department of Medicine, Division of Cardiovascular Medicine, University of Massachusetts Medical School, 368 Plantation St., AS7-1051, Worcester, MA 01605, USA; Corresponding author
Summary: The presence of nonhuman RNAs in man has been questioned and it is unclear if food-derived miRNAs cross into the circulation. In a large population study, we found nonhuman miRNAs in plasma by RNA sequencing and validated a small number of pine-pollen miRNAs by RT-qPCR in 2,776 people. The presence of these pine-pollen miRNAs associated with hay fever and not with overt cardiovascular or pulmonary disease. Using in vivo and in vitro models, we found that transmission of pollen-miRNAs into the circulation occurs via pulmonary transfer and this transfer was mediated by platelet-pulmonary vascular cell interactions and platelet pollen-DNA uptake. These data demonstrate that pollen-derived plant miRNAs can be horizontally transferred into the circulation via the pulmonary system in humans. Although these data suggest mechanistic plausibility for pulmonary-mediated plant-derived miRNA transfer into the human circulation, our large observational cohort data do not implicate major disease or risk factor association. : Biological Sciences; Molecular Biology; Omics; Transcriptomics Subject Areas: Biological Sciences, Molecular Biology, Omics, Transcriptomics
