title: Sources and Functions of Extracellular Small RNAs in Human Circulation.
abstract: Various biotypes of endogenous small RNAs (sRNAs) have been detected in human circulation, including microRNAs, transfer RNAs, ribosomal RNA, and yRNA fragments. These extracellular sRNAs (ex-sRNAs) are packaged and secreted by many different cell types. Ex-sRNAs exhibit differences in abundance in several disease states and have, therefore, been proposed for use as effective biomarkers. Furthermore, exosome-borne ex-sRNAs have been reported to elicit physiological responses in acceptor cells. Exogenous ex-sRNAs derived from diet (most prominently from plants) and microorganisms have also been reported in human blood. Essential issues that remain to be conclusively addressed concern the (a) presence and sources of exogenous ex-sRNAs in human bodily fluids, (b) detection and measurement of ex-sRNAs in human circulation, (c) selectivity of ex-sRNA export and import, (d) sensitivity and specificity of ex-sRNA delivery to cellular targets, and (e) cell-, tissue-, organ-, and organism-wide impacts of ex-sRNA-mediated cell-to-cell communication. We survey the present state of knowledge of most of these issues in this review.
authors.affiliation: Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Campus Belval, L-4367 Belvaux, Luxembourg; email: joelle.fritz@uni.lu , paul.wilmes@uni.lu.
authors.forename: Joëlle V
authors.initials: JV
authors.lastname: Fritz
authors.affiliation: Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Campus Belval, L-4367 Belvaux, Luxembourg; email: joelle.fritz@uni.lu , paul.wilmes@uni.lu.
authors.forename: Anna
authors.initials: A
authors.lastname: Heintz-Buschart
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139.
authors.forename: Anubrata
authors.initials: A
authors.lastname: Ghosal
authors.affiliation: Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Campus Belval, L-4367 Belvaux, Luxembourg; email: joelle.fritz@uni.lu , paul.wilmes@uni.lu.
authors.forename: Linda
authors.initials: L
authors.lastname: Wampach
authors.affiliation: Pacific Northwest Diabetes Research Institute, Seattle, Washington 98122.
authors.forename: Alton
authors.initials: A
authors.lastname: Etheridge
authors.affiliation: Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Campus Belval, L-4367 Belvaux, Luxembourg; email: joelle.fritz@uni.lu , paul.wilmes@uni.lu.|Pacific Northwest Diabetes Research Institute, Seattle, Washington 98122.
authors.forename: David
authors.initials: D
authors.lastname: Galas
authors.affiliation: Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Campus Belval, L-4367 Belvaux, Luxembourg; email: joelle.fritz@uni.lu , paul.wilmes@uni.lu.
authors.forename: Paul
authors.initials: P
authors.lastname: Wilmes
mesh_terms: D000818:Animals; D001692:Biological Transport; D015415:Biomarkers / Q000097:blood; D002450:Cell Communication; D004032:Diet; D000069196:Gastrointestinal Microbiome / Q000276:immunology; D005786:Gene Expression Regulation; D006790:Host-Parasite Interactions; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D035683:MicroRNAs / Q000097:blood / Q000378:metabolism; D008954:Models, Biological; D012329:RNA, Bacterial / Q000097:blood / Q000378:metabolism; D018749:RNA, Plant / Q000097:blood / Q000378:metabolism; D012335:RNA, Ribosomal / Q000097:blood* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000097:blood / Q000378:metabolism; D058727:RNA, Small Untranslated / Q000097:blood* / Q000378:metabolism; D012343:RNA, Transfer / Q000097:blood* / Q000378:metabolism; D012367:RNA, Viral / Q000097:blood / Q000378:metabolism
chemical_list: D015415:Biomarkers; D035683:MicroRNAs; D012329:RNA, Bacterial; D018749:RNA, Plant; D012335:RNA, Ribosomal; D034741:RNA, Small Interfering; D058727:RNA, Small Untranslated; D012367:RNA, Viral; D012343:RNA, Transfer
keywords: blood; gene regulation; microRNA; microorganisms; plant; vesicle