MicroRNAs Circulate in the Hemolymph of Drosophila and Accumulate Relative to Tissue MicroRNAs in an Age-Dependent Manner

Overview

Journal Genomics Insights

Publisher Sage Publications

Date 2016 Apr 5

PMID 27042094

Citations 14

Authors

Joseph M Dhahbi

Hani Atamna

Rui Li

Amy Yamakawa

Noel Guerrero

Hanh T Lam

Patricia Mote

Stephen R Spindler

Affiliations

Soon will be listed here.

Abstract

In mammals, extracellular miRNAs circulate in biofluids as stable entities that are secreted by normal and diseased tissues, and can enter cells and regulate gene expression. Drosophila melanogaster is a proven system for the study of human diseases. They have an open circulatory system in which hemolymph (HL) circulates in direct contact with all internal organs, in a manner analogous to vertebrate blood plasma. Here, we show using deep sequencing that Drosophila HL contains RNase-resistant circulating miRNAs (HL-miRNAs). Limited subsets of body tissue miRNAs (BT-miRNAs) accumulated in HL, suggesting that they may be specifically released from cells or particularly stable in HL. Alternatively, they might arise from specific cells, such as hemocytes, that are in intimate contact with HL. Young and old flies accumulated unique populations of HL-miRNAs, suggesting that their accumulation is responsive to the physiological status of the fly. These HL-miRNAs in flies may function similar to the miRNAs circulating in mammalian biofluids. The discovery of these HL-miRNAs will provide a new venue for health and disease-related research in Drosophila.

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References

Vickers K, Palmisano B, Shoucri B, Shamburek R, Remaley A . MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins. Nat Cell Biol. 2011; 13(4):423-33. PMC: 3074610. DOI: 10.1038/ncb2210. View

Kapahi P, Zid B, Harper T, Koslover D, Sapin V, Benzer S . Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway. Curr Biol. 2004; 14(10):885-90. PMC: 2754830. DOI: 10.1016/j.cub.2004.03.059. View

Cassidy J, Jha A, Posadas D, Giri R, Venken K, Ji J . miR-9a minimizes the phenotypic impact of genomic diversity by buffering a transcription factor. Cell. 2013; 155(7):1556-67. PMC: 3891883. DOI: 10.1016/j.cell.2013.10.057. View

Haselton A, Fridell Y . Insulin injection and hemolymph extraction to measure insulin sensitivity in adult Drosophila melanogaster. J Vis Exp. 2011; (52). PMC: 3197045. DOI: 10.3791/2722. View

Pandey U, Nichols C . Human disease models in Drosophila melanogaster and the role of the fly in therapeutic drug discovery. Pharmacol Rev. 2011; 63(2):411-36. PMC: 3082451. DOI: 10.1124/pr.110.003293. View

Robinson M, McCarthy D, Smyth G . edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics. 2009; 26(1):139-40. PMC: 2796818. DOI: 10.1093/bioinformatics/btp616. View

Pigati L, Yaddanapudi S, Iyengar R, Kim D, Hearn S, Danforth D . Selective release of microRNA species from normal and malignant mammary epithelial cells. PLoS One. 2010; 5(10):e13515. PMC: 2958125. DOI: 10.1371/journal.pone.0013515. View

Sondhi K . Studies in aging. II. The effects of injecting hemolymph from younger and older donors on the fecundity and the adult life span of hosts in Drosophila. J Exp Zool. 1966; 162(1):89-97. DOI: 10.1002/jez.1401620109. View

Caygill E, Johnston L . Temporal regulation of metamorphic processes in Drosophila by the let-7 and miR-125 heterochronic microRNAs. Curr Biol. 2008; 18(13):943-50. PMC: 2736146. DOI: 10.1016/j.cub.2008.06.020. View

10.

Dhahbi J, Spindler S, Atamna H, Yamakawa A, Guerrero N, Boffelli D . Deep sequencing identifies circulating mouse miRNAs that are functionally implicated in manifestations of aging and responsive to calorie restriction. Aging (Albany NY). 2013; 5(2):130-41. PMC: 3616200. DOI: 10.18632/aging.100540. View

11.

Koppen T, Weckmann A, Muller S, Staubach S, Bloch W, Dohmen R . Proteomics analyses of microvesicles released by Drosophila Kc167 and S2 cells. Proteomics. 2011; 11(22):4397-410. DOI: 10.1002/pmic.201000774. View

12.

Arroyo J, Chevillet J, Kroh E, Ruf I, Pritchard C, Gibson D . Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc Natl Acad Sci U S A. 2011; 108(12):5003-8. PMC: 3064324. DOI: 10.1073/pnas.1019055108. View

13.

Teleman A, Maitra S, Cohen S . Drosophila lacking microRNA miR-278 are defective in energy homeostasis. Genes Dev. 2006; 20(4):417-22. PMC: 1369043. DOI: 10.1101/gad.374406. View

14.

Healy N, Heneghan H, Miller N, Osborne C, Schiff R, Kerin M . Systemic mirnas as potential biomarkers for malignancy. Int J Cancer. 2012; 131(10):2215-22. DOI: 10.1002/ijc.27642. View

15.

Spindler S, Li R, Dhahbi J, Yamakawa A, Mote P, Bodmer R . Statin treatment increases lifespan and improves cardiac health in Drosophila by decreasing specific protein prenylation. PLoS One. 2012; 7(6):e39581. PMC: 3380867. DOI: 10.1371/journal.pone.0039581. View

16.

Zernecke A, Bidzhekov K, Noels H, Shagdarsuren E, Gan L, Denecke B . Delivery of microRNA-126 by apoptotic bodies induces CXCL12-dependent vascular protection. Sci Signal. 2009; 2(100):ra81. DOI: 10.1126/scisignal.2000610. View

17.

Simon A, Shih C, Mack A, Benzer S . Steroid control of longevity in Drosophila melanogaster. Science. 2003; 299(5611):1407-10. DOI: 10.1126/science.1080539. View

18.

Bartke A . Growth hormone, insulin and aging: the benefits of endocrine defects. Exp Gerontol. 2010; 46(2-3):108-11. PMC: 3408075. DOI: 10.1016/j.exger.2010.08.020. View

19.

Sondhi K . Studies in aging, 3. The physiological effects of injecting hemolymph from outbred donors into inbred hosts in Drosophila melanogaster. Proc Natl Acad Sci U S A. 1967; 57(4):965-71. PMC: 224641. DOI: 10.1073/pnas.57.4.965. View

20.

Konig A, Shcherbata H . Soma influences GSC progeny differentiation via the cell adhesion-mediated steroid-let-7-Wingless signaling cascade that regulates chromatin dynamics. Biol Open. 2015; 4(3):285-300. PMC: 4359735. DOI: 10.1242/bio.201410553. View