Sources and Functions of Extracellular Small RNAs in Human Circulation

Annual Review of Nutrition

Volumn 36, Issue , 2016, Pages 301-336

  Fritz, Joëlle V ^a   Heintz Buschart, Anna ^a   Ghosal, Anubrata ^b   Wampach, Linda ^a   Etheridge, Alton ^c   Galas, David ^a,c   Wilmes, Paul ^a  

^a UNIVERSITY OF LUXEMBOURG   (Luxembourg)

^b MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

^c PACIFIC NORTHWEST RESEARCH INSTITUTE   (United States)

Author keywords

Blood; Gene regulation; Microorganisms; MicroRNA; Plant; Vesicle

Indexed keywords

BIOLOGICAL MARKER; MICRORNA; RIBONUCLEOPROTEIN; RNA; SMALL RNA; UNCLASSIFIED DRUG; UNTRANSLATED RNA; BACTERIAL RNA; PLANT RNA; RIBOSOME RNA; SMALL INTERFERING RNA; SMALL UNTRANSLATED RNA; TRANSFER RNA; VIRUS RNA;

CELL CONTACT; DIET; EXOSOME; HUMAN; MICROORGANISM; NONHUMAN; PARASITE; PRIORITY JOURNAL; REVIEW; RNA TRANSPORT; ANIMAL; BIOLOGICAL MODEL; BLOOD; CELL COMMUNICATION; GENE EXPRESSION REGULATION; HOST PARASITE INTERACTION; HOST PATHOGEN INTERACTION; IMMUNOLOGY; INNATE IMMUNITY; INTESTINE FLORA; METABOLISM; TRANSPORT AT THE CELLULAR LEVEL;

ANIMALS; BIOLOGICAL TRANSPORT; BIOMARKERS; CELL COMMUNICATION; DIET; GASTROINTESTINAL MICROBIOME; GENE EXPRESSION REGULATION; HOST-PARASITE INTERACTIONS; HOST-PATHOGEN INTERACTIONS; HUMANS; IMMUNITY, INNATE; MICRORNAS; MODELS, BIOLOGICAL; RNA, BACTERIAL; RNA, PLANT; RNA, RIBOSOMAL; RNA, SMALL INTERFERING; RNA, SMALL UNTRANSLATED; RNA, TRANSFER; RNA, VIRAL;

EID: 84978933485     PISSN: 01999885     EISSN: 15454312     Source Type: Book Series    
DOI: 10.1146/annurev-nutr-071715-050711     Document Type: Review

References (240)

1. Abdullah Z, Schlee M, Roth S, Mraheil MA, BarchetW, et al. 2012. RIG-I detects infection with live Listeria by sensing secreted bacterial nucleic acids. EMBO J. 31(21):4153-64
2. Aird D, Ross MG, Chen W-S, Danielsson M, Fennell T, et al. 2011. Analyzing and minimizing PCR amplification bias in Illumina sequencing libraries. Genome Biol. 12(2):R18
3. Akat KM, Moore-McGriff D, Morozov P, Brown M, Gogakos T, et al. 2014. Comparative RNAsequencing analysis of myocardial and circulating small RNAs in human heart failure and their utility as biomarkers. PNAS 111(30):11151-56
4. Akay A, Sarkies P, Miska EA. 2015. E. coli OxyS non-coding RNA does not trigger RNAi in C. elegans. Sci. Rep. 5:9597
5. Akers JC, Gonda D, Kim R, Carter BS, Chen CC. 2013. Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies. J. Neuro-Oncology 113(1):1-11
6. Akers JC, Ramakrishnan V, Kim R, Skog J, Nakano I, et al. 2013. Mir-21 in the extracellular vesicles (EVs) of cerebrospinal fluid (CSF) a platform for glioblastoma biomarker development. PLOS ONE 8(10):e78115
7. Allegra A, Alonci A, Campo S, Penna G, Petrungaro A, Gerace DMC. 2012. Circulating microRNAs: new biomarkers in diagnosis, prognosis and treatment of cancer (review). Int. J. Oncol. 41(6):1897-912
8. Almanza G, Anufreichik V, Rodvold JJ, Chiu KT, DeLaney A, et al. 2013. Synthesis and delivery of short, noncoding RNA by B lymphocytes. PNAS 110(50):20182-87
9. Anders S, Huber W. 2010. Differential expression analysis for sequence count data. Genome Biol. 11(10):R106
10. Anderson MT, Seifert HS. 2011. Opportunity and means: horizontal gene transfer from the human host to a bacterial pathogen. mBio 2(1):e00005-00011
11. Anderson P, Ivanov P. 2014. tRNA fragments in human health and disease. FEBS Lett. 588(23):4297-304
12. Appaiah HN, Goswami CP, Mina L, Badve S, Sledge GW, et al. 2011. Persistent upregulation of U6:SNORD44 small RNA ratio in the serum of breast cancer patients. Breast Cancer Res. 13(5):R86
13. Archambaud C, Sismeiro O, Toedling J, Soubigou G, Bécavin C, et al. 2013. The intestinal microbiota interferes with the microRNA response upon oral Listeria infection. mBio 4(6):e00707-13
14. Arkov AL, Mankin A, Murgola EJ. 1998. An rRNA fragment and its antisense can alter decoding of genetic information. J. Bacteriol. 180(10):2744-48
15. Arroyo JD, Chevillet JR, Kroh EM, Ruf IK, Pritchard CC, et al. 2011. Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. PNAS 108(12):5003-8
16. Bahn JH, Zhang Q, Li F, Chan T-M, Lin X, et al. 2015. The landscape ofmicroRNA, PIWI-interacting RNA, and circular RNA in human saliva. Clin. Chem. 61(1):221-30
17. Bai X, Fischer S, Keshavjee S, Liu M. 2000. Heparin interference with reverse transcriptase polymerase chain reaction of RNA extracted from lungs after ischemia-reperfusion. Transpl. Int. 13(2):146-50
18. Baier SR. 2015. MicroRNAs are absorbed in biologically meaningful amounts from nutritionally relevant doses of cow's milk and chicken eggs and affect gene expression in peripheral blood mononuclear cells, cell cultures, and mouse livers. PhD Thesis, Univ. Neb., Linc. http://digitalcommons.unl.edu/nutritiondiss/50
19. Baier SR, Nguyen C, Xie F,Wood JR,Zempleni J. 2014. MicroRNAs are absorbed in biologically meaningful amounts from nutritionally relevant doses of cow milk and affect gene expression in peripheral blood mononuclear cells, HEK-293 kidney cell cultures, and mouse livers. J. Nutr. 144(10):1495-500
20. Bala S, Petrasek J, Mundkur S, Catalano D, Levin I, et al. 2012. Circulating microRNAs in exosomes indicate hepatocyte injury and inflammation in alcoholic, drug-induced, and inflammatory liver diseases. Hepatology 56(5):1946-57
21. Batagov AO, Kurochkin IV. 2013. Exosomes secreted by human cells transport largelymRNAfragments that are enriched in the 3-untranslated regions. Biol. Direct. 8:12
22. Beatty M, Guduric-Fuchs J, Brown E, Bridgett S, Chakravarthy U, et al. 2014. Small RNAs from plants, bacteria and fungi within the order Hypocreales are ubiquitous in human plasma. BMC Genom. 15:933
23. Beckett EL, Martin C, Duesing K, Jones P, Furst J, et al. 2014. VitaminDreceptor genotypemodulates the correlation between vitamin D and circulating levels of let-7a/b and vitamin D intake in an elderly cohort. J. Nutrigenetics Nutrigenomics 7(4-6):264-73
24. Biller SJ, Schubotz F, Roggensack SE, Thompson AW, Summons RE, Chisholm SW. 2014. Bacterial vesicles in marine ecosystems. Science 343(6167):183-86
25. Boeckel J-N, Thomé CE, Leistner D, Zeiher AM, Fichtlscherer S, Dimmeler S. 2013. Heparin selectively affects the quantification of microRNAs in human blood samples. Clin. Chem. 59(7):1125-27
26. Boelens MC, Wu TJ, Nabet BY, Xu B, Qiu Y, et al. 2014. Exosome transfer from stromal to breast cancer cells regulates therapy resistance pathways. Cell 159(3):499-513
27. Bomberger JM, Maceachran DP, Coutermarsh B, Ye S, O'Toole G, Stanton B. 2009. Long-distance delivery of bacterial virulence factors by Pseudomonas aeruginosa outer membrane vesicles. PLOS Pathog. 5(4):e1000382
28. Braun RE, Behringer RR, Peschon JJ, Brinster RL, Palmiter RD. 1989. Genetically haploid spermatids are phenotypically diploid. Nature 337(6205):373-76
29. Brosnan CA, Voinnet O. 2011. Cell-to-cell and long-distance siRNA movement in plants: mechanisms and biological implications. Curr. Opin. Plant Biol. 14(5):580-87
30. Brown L, Wolf JM, Prados-Rosales R, Casadevall A. 2015. Through the wall: extracellular vesicles in gram-positive bacteria, mycobacteria and fungi. Nat. Rev. Microbiol. 13(10):620-30
31. BryniarskiK, PtakW,Martin E,Nazimek K, SzczepanikM, et al. 2015. Free extracellular miRNA functionally targets cells by transfecting exosomes from their companion cells. PLOS ONE 10(4):e0122991
32. Bryzgunova OE, Laktionov PP. 2015. Extracellular nucleic acids in urine: sources, structure, diagnostic potential. Acta Nat. 7(3):48-54
33. Buck AH,Coakley G, Simbari F,McSorleyHJ, Quintana JF, et al. 2014. Exosomes secreted by nematode parasites transfer small RNAs tomammalian cells andmodulate innate immunity. Nat. Commun. 5:5488
34. Burroughs AM, Ando Y, de Hoon MJL, Tomaru Y, Suzuki H, et al. Deep-sequencing of human Argonaute-associated small RNAs provides insight into miRNA sorting and reveals Argonaute association with RNA fragments of diverse origin. RNA Biol. 8(1):158-77
35. Bustin SA, Benes V, Garson JA, Hellemans J, Huggett J, et al. 2009. The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments. Clin. Chem. 55(4):611-22
36. Bye A, Røsjø H, Aspenes ST, Condorelli G, Omland T,Wisløff U. 2013. Circulating microRNAs and aerobic fitness\-The HUNT-study. PLOS ONE 8(2):e57496
37. Carding S, Verbeke K, Vipond DT, Corfe BM, Owen LJ. 2015. Dysbiosis of the gut microbiota in disease. Microb. Ecol. Health Dis. 26:26191
38. Carthew RW, Sontheimer EJ. 2009. Origins and mechanisms of miRNAs and siRNAs. Cell 136(4):642-55
39. Chahar HS, Bao X, Casola A. 2015. Exosomes and their role in the life cycle and pathogenesis of RNA viruses. Viruses 7(6):3204-25
40. Chakrabortty SK, Prakash A, Nechooshtan G, Hearn S, Gingeras TR. 2015. Extracellular vesiclemediated transfer of processed and functional RNY5 RNA. RNA 21(11):1966-79
41. Chen X, Ba Y, Ma L, Cai X, Yin Y, et al. 2008. Characterization of microRNAs in serum a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 18(10):997-1006
42. Chen X, Liang H, Zhang J, Zen K, Zhang C-Y. 2013. MicroRNAs are ligands of Toll-like receptors. RNA 19(6):737-39
43. Cheng G, Luo R, Hu C, Cao J, Jin Y. 2013. Deep sequencing-based identification of pathogen-specific microRNAs in the plasma of rabbits infected with Schistosoma japonicum. Parasitology 140(14):1751-61
44. Chevillet JR, Kang Q, Ruf IK, Briggs HA, Vojtech LN, et al. 2014. Quantitative and stoichiometric analysis of the microRNA content of exosomes. PNAS 111(41):14888-93
45. Chiantia S, Kahya N, Ries J, Schwille P. 2006. Effects of ceramide on liquid-ordered domains investigated by simultaneous AFM and FCS. Biophys. J. 90(12):4500-8
46. Chim SS, Shing TK, Hung EC, Leung T-Y, Lau T-K, et al. 2008. Detection and characterization of placental microRNAs in maternal plasma. Clin. Chem. 54(3):482-90
47. Cocucci E, Racchetti G, Meldolesi J. 2009. Shedding microvesicles artefacts no more. Trends Cell Biol. 19(2):43-51
48. David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, et al. 2014. Diet rapidly and reproducibly alters the human gut microbiome. Nature 505(7484):559-63
49. De Boer HC, van Solingen C, Prins J, Duijs JM, HuismanMV, et al. 2013. Aspirin treatment hampers the use of plasma microRNA-126 as a biomarker for the progression of vascular disease. Eur. Heart J. 34(44):3451-57
50. De Maio A. 2011. Extracellular heat shock proteins, cellular export vesicles, and the Stress Observation System a form of communication during injury, infection, and cell damage. It is never known how far a controversial finding will go! Dedicated to Ferruccio Ritossa. Cell Stress Chaperones 16(3):235-49
51. Dhahbi JM, Spindler SR. 2013. 5-YRNA fragments derived by processing of transcripts from specific YRNA genes and pseudogenes are abundant in human serum and plasma. Physiol. Genom. 45(21):990-98
52. Dhahbi JM, Spindler SR, Atamna H, Boffelli D, Martin DI. 2014. Deep sequencing of serum small RNAs identifies patterns of 5 tRNA half and YRNA fragment expression associated with breast cancer. Biomark. Cancer 6:37-47
53. Dhahbi JM, Spindler SR, Atamna H, Yamakawa A, Boffelli D, et al. 2013. 5 tRNA halves are present as abundant complexes in serum, concentrated in blood cells, and modulated by aging and calorie restriction. BMC Genom. 14:298
54. Dickinson B, Zhang Y, Petrick JS, Heck G, Ivashuta S, Marshall WS. 2013. Lack of detectable oral bioavailability of plant microRNAs after feeding in mice. Nat. Biotechnol. 31(11):965-67
55. Duxbury MS, Ashley SW, Whang EE. 2005. RNA interference a mammalian SID-1 homologue enhances siRNA uptake and gene silencing efficacy in human cells. Biochem. Biophys. Res. Commun. 331(2):459-63
56. Ekström K, Valadi H, Sjöstrand M, Malmhäll C, Bossios A, et al. 2012. Characterization of mRNA and microRNA in human mast cell-derived exosomes and their transfer to other mast cells and blood CD34 progenitor cells. J. Extracell. Vesicles 1:18389
57. Escola JM, Kleijmeer MJ, StoorvogelW, Griffith JM, YoshieO, Geuze HJ. 1998. Selective enrichment of tetraspan proteins on the internal vesicles of multivesicular endosomes and on exosomes secreted by human B-lymphocytes. J. Biol. Chem. 273(32):20121-27
58. Etheridge A, Lee I, Hood L, Galas D, Wang K. 2011. Extracellular microRNA a new source of biomarkers. Mutat. Res. 717(1-2):85-90
59. Fabbri M, Paone A, Calore F, Galli R, Gaudio E, et al. 2012. MicroRNAs bind to Toll-like receptors to induce prometastatic inflammatory response. PNAS 109(31):E2110-16
60. Feinberg EH, Hunter CP. 2003. Transport of dsRNA into cells by the transmembrane protein SID-1. Science 301(5639):1545-47
61. Fichtlscherer S, De Rosa S, Fox H, Schwietz T, Fischer A, et al. 2010. Circulating microRNAs in patients with coronary artery disease. Circ. Res. 107(5):677-84
62. Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC. 1998. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391(6669):806-11
63. Fritz JV. 2015. Extracellular RNA in bacteria. exRNA Research Portal. Bethesda, MD: US NIH. http://exrna.org/extracellular-rna-bacteria
64. Fu X-D. 2014. Non-coding RNA a new frontier in regulatory biology. Natl. Sci. Rev. 1(2):190-204
65. Fuchs RT, Sun Z, Zhuang F, Robb GB. 2015. Bias in ligation-based small RNA sequencing library construction is determined by adaptor and RNA structure. PLOS ONE 10(5):e0126049
66. García ME, Blanco JL, Caballero J, Gargallo-Viola D. 2002. Anticoagulants interfere with PCR used to diagnose invasive aspergillosis. J. Clin. Microbiol. 40(4):1567-68
67. Garcia-Silva MR, das Neves R, Cabrera-Cabrera F, Sanguinetti J, Medeiros LC, et al. 2014. Extracellular vesicles shed by Trypanosoma cruzi are linked to small RNA pathways, life cycle regulation, and susceptibility to infection of mammalian cells. Parasitol. Res. 113(1):285-304
68. Gebetsberger J, Polacek N. 2013. Slicing tRNA to boost functional ncRNA diversity. RNA Biol. 10(12):1798-806
69. Ghosal A, Upadhyaya BB, Fritz JV, Heintz-Buschart A, Desai MS, et al. 2015. The extracellular RNA complement of Escherichia coli. Microbiol. Open 4(2):252-66
70. Gibbings DJ, Ciaudo C, ErhardtM, VoinnetO. 2009. Multivesicular bodies associate with components of miRNA effector complexes and modulate miRNA activity. Nat. Cell Biol. 11(9):1143-49
71. Grant R, Ansa-Addo E, Stratton D, Antwi-Baffour S, Jorfi S, et al. 2011. A filtration-based protocol to isolate human plasma membrane-derived vesicles and exosomes from blood plasma. J. Immunol. Methods 371(1-2):143-51
72. Groschwitz KR, Hogan SP. 2009. Intestinal barrier function: molecular regulation and disease pathogenesis. J. Allergy Clin. Immunol. 124(1):3-20
73. Guduric-Fuchs J, O'Connor A, Camp B, O'Neill CL, Medina RJ, Simpson DA. 2012. Selective extracellular vesicle-mediated export of an overlapping set of microRNAs from multiple cell types. BMC Genom. 13:357
74. Guduric-Fuchs J, O'Connor A, Cullen A, Harwood L, Medina RJ, et al. 2012. Deep sequencing reveals predominant expression of miR-21 amongst the small non-coding RNAs in retinal microvascular endothelial cells. J. Cell. Biochem. 113(6):2098-111
75. Hafner M, Renwick N, Brown M, Mihailović A, Holoch D, et al. 2011. RNA-ligase-dependent biases in miRNA representation in deep-sequenced small RNA cDNA libraries. RNA 17(9):1697-712
76. Halkein J, Tabruyn SP, Ricke-Hoch M, Haghikia A, Nguyen N-Q, et al. 2013. MicroRNA-146a is a therapeutic target and biomarker for peripartum cardiomyopathy. J. Clin. Investig. 123(5):2143-54
77. Haussecker D, Huang Y, Lau A, Parameswaran P, Fire AZ, Kay MA. 2010. Human tRNA-derived small RNAs in the global regulation of RNA silencing. RNA 16(4):673-95
78. Hebels DG, van Herwijnen MH, Brauers KJ, de Kok TM, Chalkiadaki G, et al. 2014. Elimination of heparin interference during microarray processing of fresh and biobank-archived blood samples. Environ. Mol. Mutagen. 55(6):482-91
79. Hindson CM, Chevillet JR, Briggs HA, Gallichotte EN, Ruf IK, et al. 2013. Absolute quantification by droplet digital PCR versus analog real-time PCR. Nat. Methods 10(10):1003-5
80. Hollingsworth MA, Swanson BJ. 2004. Mucins in cancer: protection and control of the cell surface. Nat. Rev. Cancer 4(1):45-60
81. Hooper LV, Littman DR,Macpherson AJ. 2012. Interactions between the microbiota and the immune system. Science 336(6086):1268-73
82. Ismail N, Wang Y, Dakhlallah D, Moldovan L, Agarwal K, et al. 2013. Macrophage microvesicles induce macrophage differentiation and miR-223 transfer. Blood 121(6):984-95
83. Ivanov P, Emara MM, Villen J, Gygi SP, Anderson P. 2011. Angiogenin-induced tRNA fragments inhibit translation initiation. Mol. Cell 43(4):613-23
84. Iwasaki YW, Siomi MC, Siomi H. 2015. PIWI-interacting RNA: its biogenesis and functions. Annu. Rev. Biochem. 84:405-33
85. Jakymiw A, Pauley KM, Li S, Ikeda K, Lian S, et al. 2007. The role ofGW/P-bodies in RNA processing and silencing. J. Cell Sci. 120(Pt 8):1317-23
86. Janas T, Janas MM, Sapoń K, Janas T. 2015. Mechanisms of RNA loading into exosomes. FEBS Lett. 589:1391-98
87. Janas T, Janas T, Yarus M. 2006. Specific RNA binding to ordered phospholipid bilayers. Nucleic Acids Res. 34(7):2128-36
88. Jayaprakash AD, Jabado O, Brown BD, Sachidanandam R. 2011. Identification and remediation of biases in the activity of RNA ligases in small-RNA deep sequencing. Nucleic Acids Res. 39(21):e141
89. Deleted in proof
90. Jiang Q,Wang Y, Hao Y, Juan L, Teng M, et al. 2009. miR2Disease a manually curated database for microRNA deregulation in human disease. Nucleic Acids Res. 37(Suppl. 1):D98-104
91. Jose AM, Garcia GA, Hunter CP. 2011. Two classes of silencing RNAs move between Caenorhabditis elegans tissues. Nat. Struct. Mol. Biol. 18(11):1184-88
92. Kamath RS, Fraser AG, Dong Y, Poulin G, Durbin R, et al. 2003. Systematic functional analysis of the Caenorhabditis elegans genome using RNAi. Nature 421(6920):231-37
93. Karere GM, Glenn JP, VandeBerg JL, Cox LA. 2012. Differential microRNA response to a highcholesterol, high-fat diet in livers of low and high LDL-C baboons. BMC Genom. 13:320
94. Kau AL, Ahern PP, GriffinNW,Goodman AL, Gordon JI. 2011. Human nutrition, the gutmicrobiome and the immune system. Nature 474(7351):327-36
95. Kirschner MB, Kao SC, Edelman JJ, Armstrong NJ, Vallely MP, et al. 2011. Haemolysis during sample preparation alters microRNA content of plasma. PLOS ONE 6(9):e24145
96. Kirschner MB, van Zandwijk N, Reid G. 2013. Cell-free microRNAs: potential biomarkers in need of standardized reporting. Front. Genet. 4:56
97. Knip M, Constantin ME, Thordal-Christensen H. 2014. Trans-kingdom cross-talk: small RNAs on the move. PLOS Genet. 10(9):e1004602
98. Kogure T, LinW-L, Yan IK, Braconi C, Patel T. 2011. Intercellular nanovesicle-mediated microRNA transfer a mechanism of environmental modulation of hepatocellular cancer cell growth. Hepatology 54(4):1237-48
99. Kogure T, Yan IK, Lin W-L, Patel T. 2013. Extracellular vesicle-mediated transfer of a novel long noncoding RNA TUC339 a mechanism of intercellular signaling in human hepatocellular cancer. Genes Cancer 4(7-8):261-72
100. Koppers-Lalic D, Hackenberg M, Bijnsdorp I, van Eijndhoven M, Sadek P, et al. 2014. Non-templated nucleotide additions distinguish the smallRNAcomposition in cells from exosomes. Cell Rep. 8(6):1649-58
101. Kosaka N, IguchiH,Hagiwara K, Yoshioka Y, Takeshita F, Ochiya T. 2013. Neutral sphingomyelinase 2 (nSMase2)-dependent exosomal transfer of angiogenic microRNAs regulate cancer cell metastasis. J. Biol. Chem. 288(15):10849-59
102. Kosaka N, Iguchi H, Ochiya T. 2010. Circulating microRNA in body fluid a new potential biomarker for cancer diagnosis and prognosis. Cancer Sci. 101(10):2087-92
103. Kosaka N, Iguchi H, Yoshioka Y, Hagiwara K, Takeshita F, Ochiya T. 2012. Competitive interactions of cancer cells and normal cells via secretory microRNAs. J. Biol. Chem. 287(2):1397-405
104. Kosaka N, Iguchi H, Yoshioka Y, Takeshita F, Matsuki Y, Ochiya T. 2010. Secretory mechanisms and intercellular transfer of microRNAs in living cells. J. Biol. Chem. 285(23):17442-52
105. Kosaka N, IzumiH, Sekine K,Ochiya T. 2010. MicroRNA as a new immune-regulatory agent in breast milk. Silence 1(1):7
106. Kroh EM, Parkin RK, Mitchell PS, Tewari M. 2010. Analysis of circulating microRNA biomarkers in plasma and serum using quantitative reverse transcription-PCR (qRT-PCR). Methods 50(4):298-301
107. Lagos-Quintana M, Rauhut R, Yalcin A, Meyer J, Lendeckel W, Tuschl T. 2002. Identification of tissue-specific microRNAs from mouse. Curr. Biol. 12(9):735-39
108. Lara PC, Pruschy M, ZimmermannM,Henríquez-Hernández LA. 2011. MVP and vaults a role in the radiation response. Radiat. Oncol. 6:148
109. Lasda E, Parker R. 2014. Circular RNAs: diversity of form and function. RNA 20(12):1829-42
110. Lawrie CH, Gal S, Dunlop HM, Pushkaran B, Liggins AP, et al. 2008. Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br. J.Haematol. 141(5):672-75
111. Lee LW, Zhang S, Etheridge A, Ma L, Martin D, et al. 2010. Complexity of the microRNA repertoire revealed by next-generation sequencing. RNA 16(11):2170-80
112. Lee YJ, Kim V, Muth DC, Witwer KW. 2015. Validated microRNA target databases an evaluation. Drug Dev. Res 76(7):389-96
113. Lehmann SM, Krüger C, Park B, Derkow K, Rosenberger K, et al. 2012. An unconventional role for miRNA: Let-7 activates Toll-like receptor 7 and causes neurodegeneration. Nat. Neurosci. 15(6):827-35
114. Leidner RS, Li L, Thompson CL. 2013. Dampening enthusiasm for circulating microRNA in breast cancer. PLOS ONE 8(3):e57841
115. Li Y, Qiu C, Tu J, Geng B, Yang J, et al. 2014. HMDD v2.0 a database for experimentally supported human microRNA and disease associations. Nucleic Acids Res. 42(Suppl. 1):D1070-74
116. Li Z, Ender C, Meister G, Moore PS, Chang Y, John B. 2012. Extensive terminal and asymmetric processing of small RNAs from rRNAs, snoRNAs, snRNAs, and tRNAs. Nucleic Acids Res. 40(14):6787-99
117. Liang H, Zhang S, Fu Z, Wang Y, Wang N, et al. 2015. Effective detection and quantification of dietetically absorbed plant microRNAs in human plasma. J. Nutr. Biochem. 26(5):505-12
118. Lim PK, Bliss SA, Patel SA, Taborga M, Dave MA, et al. 2011. Gap junction-mediated import of microRNA from bone marrow stromal cells can elicit cell cycle quiescence in breast cancer cells. Cancer Res. 71(5):1550-60
119. Liu H,Wang X,Wang H-D,Wu J, Ren J, et al. 2012. Escherichia coli noncoding RNAs can affect gene expression and physiology of Caenorhabditis elegans. Nat. Commun. 3:1073
120. Liu S, da Cunha AP, Rezende RM, Cialic R, Wei Z, et al. 2016. The host shapes the gut microbiota via fecal microRNA. Cell Host Microbe 19(1):32-43
121. Mangan PR,Harrington LE, O'Quinn DB, HelmsWS, Bullard DC, et al. 2006. Transforming growth factor-βinduces development of the TH17 lineage. Nature 441(7090):231-34
122. Mao Y-B, Xue X-Y, Tao X-Y, Yang C-Q, Wang L-J, Chen X-Y. 2013. Cysteine protease enhances plant-mediated bollworm RNA interference. Plant Mol. Biol. 83(1-2):119-29
123. Martí E, PantanoL,Banez-CoronelM, Llorens F, Minones-Moyano E, et al. 2010. Amyriad of miRNA variants in control and Huntington's disease brain regions detected by massively parallel sequencing. Nucleic Acids Res. 38(20):7219-35
124. Marz M, Gruber AR, Höner Siederdissen C, Amman F, Badelt S, et al. 2011. Animal snoRNAs and scaRNAs with exceptional structures. RNA Biol. 8(6):938-46
125. Meckes DG, Shair KHY, Marquitz AR, Kung C-P, Edwards RH, Raab-Traub N. 2010. Human tumor virus utilizes exosomes for intercellular communication. PNAS 107(47):20370-75
126. Melnik BC. 2015. Milk an epigenetic amplifier of FTO-mediated transcription? Implications forWestern diseases. J. Transl. Med. 13(1):385
127. Mishima E, Inoue C, Saigusa D, Inoue R, Ito K, et al. 2014. Conformational change in transfer RNA is an early indicator of acute cellular damage. J. Am. Soc. Nephrol. 25(10):2316-26
128. Mitchell PS, Parkin RK, Kroh EM, Fritz BR,Wyman SK, et al. 2008. Circulating microRNAs as stable blood-based markers for cancer detection. PNAS 105(30):10513-18
129. Mittelbrunn M, Gutiérrez-Vázquez C, Villarroya-Beltri C, González S, Sánchez-Cabo F, et al. 2011. Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells. Nat. Commun. 2:282
130. Mittelbrunn M, Sánchez-Madrid F. 2012. Intercellular communication: diverse structures for exchange of genetic information. Nat. Rev. Mol. Cell Biol. 13(5):328-35
131. Mlotshwa S, Pruss GJ, MacArthur JL, Endres MW, Davis C, et al. 2015. A novel chemopreventive strategy based on therapeutic microRNAs produced in plants. Cell Res. 25(4):521-24
132. Montecalvo A,Larregina AT, ShufeskyWJ, StolzDB, SullivanMLG,et al. 2012. Mechanism of transfer of functional microRNAs between mouse dendritic cells via exosomes. Blood 119(3):756-66
133. Morel L, Regan M, HigashimoriH,Ng SK, EsauC, et al. 2013. Neuronal exosomal miRNA-dependent translational regulation of astroglial glutamate transporter GLT1. J. Biol. Chem. 288(10):7105-16
134. Mulcahy LA, Pink RC, Carter DRF. 2014. Routes and mechanisms of extracellular vesicle uptake. J. Extracell. Vesicles 3:3
135. Munafó DB, Robb GB. 2010. Optimization of enzymatic reaction conditions for generating representative pools of cDNA from small RNA. RNA 16(12):2537-52
136. Narayanan A, Iordanskiy S, Das R, Van Duyne R, Santos S, et al. 2013. Exosomes derived from HIV-1-infected cells contain trans-activation response element RNA. J. Biol. Chem. 288(27):20014-33
137. Nguyen VT, Kiss T,Michels AA, Bensaude O. 2001. 7SK small nuclear RNA binds to and inhibits the activity of CDK9/cyclin T complexes. Nature 414(6861):322-25
138. Nicola AM, Frases S, Casadevall A. 2009. Lipophilic dye staining of Cryptococcus neoformans extracellular vesicles and capsule. Eukaryot. Cell 8(9):1373-80
139. NIH (Natl. Inst. Health). 2016. Extracellular RNA Communication Consortium. Bethesda,MD: USNIH. http://exrna.org
140. Nolte-Hoen EN, Buermans HP, Waasdorp M, Stoorvogel W, Wauben MH, Hoen PA. 2012. Deep sequencing of RNA from immune cell-derived vesicles uncovers the selective incorporation of small non-coding RNA biotypes with potential regulatory functions. Nucleic Acids Res. 40(18):9272-85
141. Obregón-Henao A,Duque-CorreaM, Rojas M, García LF, Brennan PJ, et al. 2012. Stable extracellular RNA fragments of Mycobacterium tuberculosis induce early apoptosis in humanmonocytes via a caspase-8 dependent mechanism. PLOS ONE 7(1):e29970
142. Oldenburg M, Krüger A, Ferstl R, Kaufmann A, Nees G, et al. 2012. TLR13 recognizes bacterial 23s rRNA devoid of erythromycin resistance-forming modification. Science 337(6098):1111-15
143. Oliveira DL, Freire-Lima CG, Nosanchuk JD, Casadevall A, Rodrigues ML, Nimrichter L. 2010. Extracellular vesicles from Cryptococcus neoformans modulate macrophage functions. Infect. Immun. 78(4):1601-9
144. Page K, Guttery DS, Zahra N, Primrose L, Elshaw SR, et al. 2013. Influence of plasma processing on recovery and analysis of circulating nucleic acids. PLOS ONE 8(10):e77963
145. Park K-S, Choi K-H, Kim Y-S, Hong BS, Kim OY, et al. 2010. Outer membrane vesicles derived from Escherichia coli induce systemic inflammatory response syndrome. PLOS ONE 5(6):e11334
146. Parker H, Chitcholtan K,Hampton MB, Keenan JI. 2010. Uptake of Helicobacter pylori outer membrane vesicles by gastric epithelial cells. Infect. Immun. 78(12):5054-61
147. Patton JG, Franklin JL, Weaver AM, Vickers K, Zhang B, et al. 2015. Biogenesis, delivery, and function of extracellular RNA. J. Extracell. Vesicles 1:27494
148. Pegtel DM, Cosmopoulos K, Thorley-Lawson DA, van Eijndhoven MA, Hopmans ES, et al. 2010. Functional delivery of viral miRNAs via exosomes. PNAS 107(14):6328-33
149. Peres da Silva R, Puccia R, Rodrigues ML, Oliveira DL, Joffe LS, et al. 2015. Extracellular vesiclemediated export of fungal RNA. Sci. Rep. 5:7763
150. Plieskatt JL, Feng Y, Rinaldi G, Mulvenna JP, Bethony JM, Brindley PJ. 2014. Circumventing qPCR inhibition to amplify miRNAs in plasma. Biomark. Res. 2:13
151. Puppa MJ, White JP, Sato S, Cairns M, Baynes JW, Carson JA. 2011. Gut barrier dysfunction in the APCMin/+ mouse model of colon cancer cachexia. Biochim. Biophys. Acta. 1812(12):1601-6
152. Quinn JF, Patel T, Wong D, Das S, Freedman JE, et al. 2015. Extracellular RNAs: development as biomarkers of human disease. J. Extracell. Vesicles 4:27495
153. Quintana JF, Makepeace BL, Babayan SA, Ivens A, Pfarr KM, et al. 2015. Extracellular onchocercaderived small RNAs in host nodules and blood. Parasites Vectors 8:58
154. RaposoG, StoorvogelW. 2013. Extracellular vesicles: exosomes,microvesicles, and friends. J. Cell Biol. 200(4):373-83
155. Ratajczak J, Miekus K, Kucia M, Zhang J,RecaR, et al. 2006. Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: evidence for horizontal transfer of mRNA and protein delivery. Leukemia 20(5):847-56
156. Rekker K, Saare M, Roost AM, Kubo A-L, Zarovni N, et al. 2014. Comparison of serum exosome isolation methods for microRNA profiling. Clin. Biochem. 47(1-2):135-38
157. Resnick KE, Alder H, Hagan JP, Richardson DL, Croce CM, Cohn DE. 2009. The detection of differentially expressed microRNAs from the serum of ovarian cancer patients using a novel real-time PCR platform. Gynecol. Oncol. 112(1):55-59
158. RidderK,Keller S,DamsM,Rupp A-K, Schlaudraff J, et al. 2014. Extracellular vesicle-mediated transfer of genetic information between the hematopoietic system and the brain in response to inflammation. PLOS Biol. 12(6):e1001874
159. Risso D, Ngai J, Speed TP, Dudoit S. 2014. Normalization of RNA-seq data using factor analysis of control genes or samples. Nat. Biotechnol. 32(9):896-902
160. Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, et al. 2015. Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 43(7):e47
161. Rome S. 2015. Use of miRNAs in biofluids as biomarkers in dietary and lifestyle intervention studies. Genes Nutr. 10(5):33
162. Romilly C, Lays C, Tomasini A, Caldelari I, Benito Y, et al. 2014. A non-coding RNA promotes bacterial persistence and decreases virulence by regulating a regulator in Staphylococcus aureus. PLOS Pathog. 10(3):e1003979
163. Rosa A, Brivanlou AH. 2009. MicroRNAs in early vertebrate development. Cell Cycle 8(21):3513-20
164. Rosenblad MA, Larsen N, Samuelsson T, Zwieb C. 2014. Kinship in the SRP RNA family. RNA Biol. 6(5):508-16
165. Roume H, Muller EEL, Cordes T, Renaut J, Hiller K, Wilmes P. 2013. A biomolecular isolation framework for eco-systems biology. ISME J. 7(1):110-21
166. Russo F. 2015. miRandola database: the future of non-invasive diagnosis through circulating RNA biomarkers. Extracellular RNA Communication Consortium. Bethesda, MD: US NIH. http:// exrna.org/miran-dola-database-The-future-of-non-invasive-diagnosis-through-circulating-rnabiomarkers
167. Ryu M-S, Langkamp-Henken B, Chang S-M, Shankar MN, Cousins RJ. 2011. Genomic analysis, cytokine expression, and microRNA profiling reveal biomarkers of human dietary zinc depletion and homeostasis. PNAS 108(52):20970-75
168. Salter SJ, Cox MJ, Turek EM, Calus ST, CooksonWO, et al. 2014. Reagent and laboratory contamination can critically impact sequence-based microbiome analyses. BMC Biol. 12(1):87
169. Samson JE, Magadán AH, Sabri M, Moineau S. 2013. Revenge of the phages: defeating bacterial defences. Nat. Rev. Microbiol. 11(10):675-87
170. Sana J, Faltejskova P, Svoboda M, Slaby O. 2012. Novel classes of non-coding RNAs and cancer. J. Transl. Med. 10(1):103
171. Sato-Kuwabara Y, Melo SA, Soares FA, Calin GA. 2014. The fusion of two worlds: non-coding RNAs and extracellular vesicles-diagnostic and therapeutic implications (Review). Int. J. Oncol. 46(1):17-27
172. Schwechheimer C, Kuehn MJ. 2015. Outer-membrane vesicles from Gram-negative bacteria: biogenesis and functions. Nat. Rev. Microbiol. 13(10):605-19
173. Semenov D V, Baryakin DN, Brenner E V, Kurilshikov AM, Vasiliev GV, et al. 2012. Unbiased approach to profile the variety of small non-coding RNA of human blood plasma with massively parallel sequencing technology. Expert Opin. Biol. Ther. 12(Suppl. 1):S43-51
174. Sewer A, Gubian S, Kogel U, Veljkovic E, Han W, et al. 2014. Assessment of a novel multi-array normalization method based on spike-in control probes suitable for microRNA datasets with global decreases in expression. BMC Res. Notes 7:302
175. ShaoY, FengL,Rutherford ST, PapenfortK,Bassler BL. 2013. Functional determinants of the quorumsensing non-coding RNAs and their roles in target regulation. EMBO J. 32(15):2158-71
176. Sharifpanah F, Jayarathne SWG, Bekhite MM, Hurtado-Oliveros J, Preissner KT, et al. 2015. Stimulation of vasculogenesis and leukopoiesis of embryonic stem cells by extracellular transfer RNA and ribosomal RNA. Free Radic. Biol. Med. 89:1203-17
177. Shen J, Stass SA, Jiang F. 2013. MicroRNAs as potential biomarkers in human solid tumors. Cancer Lett. 329(2):125-36
178. Shen Y, Giardino Torchia ML, Lawson GW, Karp CL, Ashwell JD, Mazmanian SK. 2012. Outer membrane vesicles of a human commensal mediate immune regulation and disease protection. Cell Host Microbe 12(4):509-20
179. Shih JD, Hunter CP. 2011. SID-1 is a dsRNA-selective dsRNA-gated channel. RNA 17(6):1057-65
180. Skog J, Wurdinger T, Rijn SV, Meijer D, Gainche L, et al. 2012. Glioblastoma microvesicles transport RNA and protein that promote tumor growth and provide diagnostic biomarkers. Nat. Cell Biol. 10(12):1470-76
181. Snow JW, Hale AE, Isaacs SK, Baggish AL, Chan SY. 2013. Ineffective delivery of diet-derived micro-RNAs to recipient animal organisms. RNA Biol. 10(7):1107-16
182. Sobala A, Hutvagner G. 2013. Small RNAs derived from the 5 end of tRNA can inhibit protein translation in human cells. RNA Biol. 10(4):553-63
183. Squadrito ML, Baer C, Burdet F, Maderna C, Gilfillan GD, et al. 2014. Endogenous RNAs modulate microRNA sorting to exosomes and transfer to acceptor cells. Cell Rep. 8:1432-46
184. Tabet F, Vickers KC, Cuesta-Torres LF, Wiese Carrie B, Shoucri BM, et al. 2012. HDL-transferred microRNA-223 regulates ICAM-1 expression in endothelial cells. Nat. Commun. 29(6):997-1003
185. Tarallo S, Pardini B,Mancuso G, Rosa F, Di Gaetano C, et al. 2014. MicroRNA expression in relation to different dietary habits a comparison in stool and plasma samples. Mutagenesis 29(5):385-91
186. Théry C, Ostrowski M, Segura E. 2009. Membrane vesicles as conveyors of immune responses. Nat. Rev. Immunol. 9(8):581-93
187. Title AC, Denzler R, Stoffel M. 2015. Uptake and function studies of maternal milk-derived micro-RNAs. J. Biol. Chem. 290(39)23680-91
188. Tosar JP, Gambaro F, Sanguinetti J, Bonilla B, Witwer KW, Cayota A. 2015. Assessment of small RNAsorting into different extracellular fractions revealed by high-throughput sequencing of breast cell lines. Nucleic Acids Res. 43(11)5601-16
189. Trapnell C, Hendrickson DG, Sauvageau M, Goff L, Rinn JL, Pachter L. 2013. Differential analysis of gene regulation at transcript resolution with RNA-seq. Nat. Biotechnol. 31(1):46-53
190. Tsui NB, Ng EK, Lo YM. 2002. Stability of endogenous and added RNA in blood specimens, serum, and plasma. Clin. Chem. 48(10):1647-53
191. Tsuji E, Hiki N, Nomura S, Fukushima R, Kojima J, et al. 2003. Simultaneous onset of acute inflammatory response, sepsis-like symptoms and intestinal mucosal injury after cancer chemotherapy. Int. J. Cancer. 107(2):303-8
192. Turchinovich A, Samatov TR, Tonevitsky AG, Burwinkel B. 2013. Circulating miRNAs: cell-cell communication function? Front. Genet. 4:119
193. Turchinovich A, Weiz L, Burwinkel B. 2012. Extracellular miRNAs: the mystery of their origin and function. Trends Biochem. Sci. 37(11):460-65
194. Turchinovich A, Weiz L, Langheinz A, Burwinkel B. 2011. Characterization of extracellular circulating microRNA. Nucleic Acids Res. 39(16):7223-33
195. Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO. 2007. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat. Cell Biol. 9(6):654-59
196. Van Balkom BWM, Eisele AS, PegtelDM, Bervoets S, Verhaar MC. 2015. Quantitative and qualitative analysis of small RNAs in human endothelial cells and exosomes provides insights into localized RNA processing, degradation and sorting. J. Extracell. Vesicles 4:26760
197. Van der Pol E, Böing AN, Harrison P, Sturk A, Nieuwland R. 2012. Classification, functions, and clinical relevance of extracellular vesicles. Pharmacol. Rev. 64(3):676-705
198. Van Deun J, Mestdagh P, Sormunen R, Cocquyt V, Vermaelen K, et al. 2014. The impact of disparate isolation methods for extracellular vesicles on downstream RNA profiling. J. Extracell. Vesicles 3:24858
199. Vickers KC, Palmisano BT, Shoucri BM, Shamburek RD, Remaley AT. 2011. MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins. Nat. Cell Biol. 13(4):423-33
200. Vickers KC, Roteta LA, Hucheson-Dilks H, Han L, Guo Y. 2015. Mining diverse small RNA species in the deep transcriptome. Trends Biochem. Sci. 40(1):4-7
201. Villarroya-BeltriC,Baixauli F, Gutiérrez-VázquezC, Sánchez-Madrid F,Mittelbrunn M. 2014. Sorting it out: regulation of exosome loading. Semin. Cancer Biol. 28:3-13
202. Villarroya-Beltri C, Gutiérrez-Vázquez C, Sánchez-Cabo F, Pérez-Hernández D, Vázquez J, et al. 2013. Sumoylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding to specific motifs. Nat. Commun. 4:2980
203. Voellenkle C, Rooij JV, Guffanti A, Brini E, Fasanaro P, et al. 2012. Deep-sequencing of endothelial cells exposed to hypoxia reveals the complexity of known and novel microRNAs. RNA 18(3):472-84
204. Wagner J, RiwantoM, Besler C, Knau A, Fichtlscherer S, et al. 2013. Characterization of levels and cellular transfer of circulating lipoprotein-bound microRNAs. Arterioscler. Thromb. Vasc. Biol. 33(6):1392-400
205. Wang H, Li X, Wang C, Zhu D, Xu Y. 2014. Abnormal ultrastructure of intestinal epithelial barrier in mice with alcoholic steatohepatitis. Alcohol 48(8):787-93
206. Wang K, Li H, Yuan Y, Etheridge A, Zhou Y, et al. 2012. The complex exogenous RNA spectra in human plasma an interface with human gut biota? PLOS ONE 7(12):e51009
207. Wang K, Yuan Y, Cho J-H, McClarty S, Baxter D, Galas DJ. 2012. Comparing the microRNA spectrum between serum and plasma. PLOS ONE 7(7):e41561
208. Wang K, Yuan Y, Li H, Cho J-H, Huang D, et al. 2013. The spectrum of circulating RNA a window into systems toxicology. Toxicol. Sci. 132(2):478-92
209. Wang K, Zhang S, Marzolf B, Troisch P, Brightman A, et al. 2009. Circulating microRNAs, potential biomarkers for drug-induced liver injury. PNAS 106(11):4402-7
210. Wang K, Zhang S,Weber J, Baxter D, Galas DJ. 2010. Export ofmicroRNAs and microRNA-protective protein by mammalian cells. Nucleic Acids Res. 38(20):7248-59
211. Wang W, Shi Q, MattesWB, Mendrick DL, Yang X. 2015. Translating extracellular microRNA into clinical biomarkers for drug-induced toxicity: from high-throughput profiling to validation. Biomark. Med. 9(11):1177-88
212. Wang Y, Tong J, Chang B,Wang B, Zhang D, Wang B. 2014. Effects of alcohol on intestinal epithelial barrier permeability and expression of tight junction-associated proteins. Mol. Med. Rep. 9(6):2352-56
213. Wang Y-T, Tsai P-C, Liao Y-C, HsuC-Y, Juo S-H. 2013. CirculatingmicroRNAs have a sex-specific association with metabolic syndrome. J. Biomed. Sci. 20:72
214. Weber JA, Baxter DH, Zhang S, Huang DY, Huang KH, et al. 2010. The microRNA spectrum in 12 body fluids. Clin. Chem. 56(11):1733-41
215. Wild K, Sinning I, Cusack S. 2001. Crystal structure of an early protein-RNA assembly complex of the signal recognition particle. Science 294(5542):598-601
216. Williams Z, Ben-Dov IZ, Elias R, Mihailovic A, Brown M, et al. 2013. Comprehensive profiling of circulating microRNA via small RNA sequencing of cDNA libraries reveals biomarker potential and limitations. PNAS 110(11):4255-60
217. Winston WM, Molodowitch C, Hunter CP. 2002. Systemic RNAi in C. elegans requires the putative transmembrane protein SID-1. Science 295(5564):2456-59
218. Witwer KW. 2015. Contamination or artifacts may explain reports of plant miRNAs in humans. J. Nutr. Biochem. 26(12):1685
219. Witwer KW. 2015. Circulating microRNA biomarker studies: pitfalls and potential solutions. Clin. Chem. 61(1):56-63
220. Witwer KW, Buzás EI, Bemis LT, Bora A, Lässer C, et al. 2013. Standardization of sample collection, isolation and analysis methods in extracellular vesicle research. J. Extracell. Vesicles 2:20360
221. Witwer KW, Hirschi KD. 2014. Transfer and functional consequences of dietary microRNAs in vertebrates: concepts in search of corroboration. BioEssays 36(4):394-406
222. Witwer KW, McAlexander MA, Queen SE, Adams RJ. 2013. Real-time quantitative PCR and droplet digital PCR for plant miRNAs in mammalian blood provide little evidence for general uptake of dietary miRNAs: limited evidence for general uptake of dietary plant xenomiRs. RNA Biol. 10(7):1080-86
223. Wurdinger T, Gatson NN, Balaj L, Kaur B, Breakefield XO, Pegtel DM. 2012. Extracellular vesicles and their convergence with viral pathways. Adv. Virol. 2012(1):767694
224. Xiang S, Fruehauf J, Li CJ. 2006. Short hairpin RNA-expressing bacteria elicit RNA interference in mammals. Nat. Biotechnol. 24(6):697-702
225. Yang J, Farmer LM, Agyekum AA, Hirschi KD. 2015. Detection of dietary plant-based small RNAs in animals. Cell Res. 25:517-20
226. Yao B, La LB, Chen Y-C, Chang L-J, Chan EKL. 2012. Defining a new role of GW182 in maintaining miRNA stability. EMBO Rep. 13(12):1102-8
227. Yarmishyn AA, Kurochkin I V. 2015. Long noncoding RNAs a potential novel class of cancer biomarkers. Front. Genet. 6:145
228. Yoo B-C, Kragler F, Varkonyi-Gasic E, Haywood V, Archer-Evans S, et al. 2004. A systemic small RNA signaling system in plants. Plant Cell 16(8):1979-2000
229. Yu B, Yang Z, Li J, Minakhina S, YangM, et al. 2005. Methylation as a crucial step in plant microRNA biogenesis. Science 307(5711):932-35
230. Yuan S, Tang H, Xing J, Fan X, Cai X, et al. 2014. Methylation by NSun2 represses the levels and function of microRNA 125b. Mol. Cell Biol. 34(19):3630-41
231. Zempleni J, Baier SR, Hirschi K. 2015. Diet-responsive microRNAs are likely exogenous. J. Biol. Chem. 290(41):25197
232. Zernecke A, Bidzhekov K, Noels H, Shagdarsuren E, Gan L, et al. 2009. Delivery of microRNA-126 by apoptotic bodies induces CXCL12-dependent vascular protection. Sci. Signal. 2(100):ra81
233. Zhang L, Hou D, Chen X, Li D, Zhu L, et al. 2012. Exogenous plant MIR168a specifically targets mammalian LDLRAP1: evidence of cross-kingdom regulation by microRNA. Cell Res. 22(1):107-26
234. Zhang Y, Liu D, Chen X, Li J, Li L, et al. 2010. Secreted monocytic miR-150 enhances targeted endothelial cell migration. Mol. Cell 39(1):133-44
235. Zhang Y, Wiggins B, Lawrence C, Petrick J, Ivashuta S, Heck G. 2012. Analysis of plant-derived miRNAs in animal small RNA datasets. BMC Genom. 13(1):381
236. Zhou W, Fong MY, Min Y, Somlo G, Liu L, et al. 2014. Cancer-secreted miR-105 destroys vascular endothelial barriers to promote metastasis. Cancer Cell 25(4):501-15
237. Zhou Z, Li X, Liu J, Dong L, Chen Q, et al. 2014. Honeysuckle-encoded atypical microRNA2911 directly targets influenza A viruses. Cell Res. 25(1):39-49
238. Zhu W, Qin W, Atasoy U, Sauter ER. 2009. Circulating microRNAs in breast cancer and healthy subjects. BMC Res. Notes 2:89
239. Zhuang F, Fuchs RT, Robb GB. 2012. SmallRNAexpression profiling by high-throughput sequencing: implications of enzymatic manipulation. J. Nucleic Acids 2012:360358
240. Zhuang F, Fuchs RT, Sun Z, Zheng Y, Robb GB. 2012. Structural bias in T4 RNA ligase-mediated 3-adapter ligation. Nucleic Acids Res. 40(7):e54