MicroRNA-Dependent Transcriptional Silencing of Transposable Elements in Drosophila Follicle Cells

Overview

Journal PLoS Genet

Specialty Genetics

Date 2015 May 21

PMID 25993106

Citations 11

Authors

Bruno Mugat

Abdou Akkouche

Vincent Serrano

Claudia Armenise

Blaise Li

Christine Brun

Tudor A Fulga

David Van Vactor

Alain Pelisson

Severine Chambeyron

Affiliations

Soon will be listed here.

Abstract

RNA interference-related silencing mechanisms concern very diverse and distinct biological processes, from gene regulation (via the microRNA pathway) to defense against molecular parasites (through the small interfering RNA and the Piwi-interacting RNA pathways). Small non-coding RNAs serve as specificity factors that guide effector proteins to ribonucleic acid targets via base-pairing interactions, to achieve transcriptional or post-transcriptional regulation. Because of the small sequence complementarity required for microRNA-dependent post-transcriptional regulation, thousands of microRNA (miRNA) putative targets have been annotated in Drosophila. In Drosophila somatic ovarian cells, genomic parasites, such as transposable elements (TEs), are transcriptionally repressed by chromatin changes induced by Piwi-interacting RNAs (piRNAs) that prevent them from invading the germinal genome. Here we show, for the first time, that a functional miRNA pathway is required for the piRNA-mediated transcriptional silencing of TEs in this tissue. Global miRNA depletion, caused by tissue- and stage-specific knock down of drosha (involved in miRNA biogenesis), AGO1 or gawky (both responsible for miRNA activity), resulted in loss of TE-derived piRNAs and chromatin-mediated transcriptional de-silencing of TEs. This specific TE de-repression was also observed upon individual titration (by expression of the complementary miRNA sponge) of two miRNAs (miR-14 and miR-34) as well as in a miR-14 loss-of-function mutant background. Interestingly, the miRNA defects differentially affected TE- and 3' UTR-derived piRNAs. To our knowledge, this is the first indication of possible differences in the biogenesis or stability of TE- and 3' UTR-derived piRNAs. This work is one of the examples of detectable phenotypes caused by loss of individual miRNAs in Drosophila and the first genetic evidence that miRNAs have a role in the maintenance of genome stability via piRNA-mediated TE repression.

Citing Articles

Transposable Element Expression Profiles in Premalignant Pigment Cell Lesions and Melanoma of Xiphophorus.

Munch L, Helmprobst F, Volff J, Chalopin D, Schartl M, Kneitz S Genes (Basel). 2024; 15(5).

PMID: 38790249 PMC: 11121471. DOI: 10.3390/genes15050620.

What Have We Learned in 30 Years of Investigations on Transposons?.

Palazzo A, Caizzi R, Moschetti R, Marsano R Cells. 2022; 11(3).

PMID: 35159391 PMC: 8834629. DOI: 10.3390/cells11030583.

The Mi-2 nucleosome remodeler and the Rpd3 histone deacetylase are involved in piRNA-guided heterochromatin formation.

Mugat B, Nicot S, Varela-Chavez C, Jourdan C, Sato K, Basyuk E Nat Commun. 2020; 11(1):2818.

PMID: 32499524 PMC: 7272611. DOI: 10.1038/s41467-020-16635-5.

MicroRNAs Regulate Multiple Aspects of Locomotor Behavior in .

Donelson N, Dixit R, Pichardo-Casas I, Chiu E, Ohman R, Slawson J G3 (Bethesda). 2019; 10(1):43-55.

PMID: 31694853 PMC: 6945011. DOI: 10.1534/g3.119.400793.

as a Model to Study the Multiple Phenotypes, Related to Genome Stability of the Fragile-X Syndrome.

Specchia V, Puricella A, DAttis S, Massari S, Giangrande A, Bozzetti M Front Genet. 2019; 10:10.

PMID: 30815010 PMC: 6381874. DOI: 10.3389/fgene.2019.00010.

References

Azzam G, Smibert P, Lai E, Liu J . Drosophila Argonaute 1 and its miRNA biogenesis partners are required for oocyte formation and germline cell division. Dev Biol. 2012; 365(2):384-94. PMC: 3763516. DOI: 10.1016/j.ydbio.2012.03.005. View

Le Thomas A, Rogers A, Webster A, Marinov G, Liao S, Perkins E . Piwi induces piRNA-guided transcriptional silencing and establishment of a repressive chromatin state. Genes Dev. 2013; 27(4):390-9. PMC: 3589556. DOI: 10.1101/gad.209841.112. View

Darricarrere N, Liu N, Watanabe T, Lin H . Function of Piwi, a nuclear Piwi/Argonaute protein, is independent of its slicer activity. Proc Natl Acad Sci U S A. 2013; 110(4):1297-302. PMC: 3557079. DOI: 10.1073/pnas.1213283110. View

Kheradpour P, Stark A, Roy S, Kellis M . Reliable prediction of regulator targets using 12 Drosophila genomes. Genome Res. 2007; 17(12):1919-31. PMC: 2099599. DOI: 10.1101/gr.7090407. View

Grentzinger T, Chambeyron S . Fast and accurate method to purify small noncoding RNAs from Drosophila ovaries. Methods Mol Biol. 2013; 1093:171-82. DOI: 10.1007/978-1-62703-694-8_14. View

Park J, Liu X, Strauss T, McKearin D, Liu Q . The miRNA pathway intrinsically controls self-renewal of Drosophila germline stem cells. Curr Biol. 2007; 17(6):533-8. DOI: 10.1016/j.cub.2007.01.060. View

Macias S, Plass M, Stajuda A, Michlewski G, Eyras E, Caceres J . DGCR8 HITS-CLIP reveals novel functions for the Microprocessor. Nat Struct Mol Biol. 2012; 19(8):760-6. PMC: 3442229. DOI: 10.1038/nsmb.2344. View

Muerdter F, Guzzardo P, Gillis J, Luo Y, Yu Y, Chen C . A genome-wide RNAi screen draws a genetic framework for transposon control and primary piRNA biogenesis in Drosophila. Mol Cell. 2013; 50(5):736-48. PMC: 3724422. DOI: 10.1016/j.molcel.2013.04.006. View

Eden E, Navon R, Steinfeld I, Lipson D, Yakhini Z . GOrilla: a tool for discovery and visualization of enriched GO terms in ranked gene lists. BMC Bioinformatics. 2009; 10:48. PMC: 2644678. DOI: 10.1186/1471-2105-10-48. View

10.

Ketting R . The many faces of RNAi. Dev Cell. 2011; 20(2):148-61. DOI: 10.1016/j.devcel.2011.01.012. View

11.

Klenov M, Lavrov S, Korbut A, Stolyarenko A, Yakushev E, Reuter M . Impact of nuclear Piwi elimination on chromatin state in Drosophila melanogaster ovaries. Nucleic Acids Res. 2014; 42(10):6208-18. PMC: 4041442. DOI: 10.1093/nar/gku268. View

12.

Flynt A, Lai E . Biological principles of microRNA-mediated regulation: shared themes amid diversity. Nat Rev Genet. 2008; 9(11):831-42. PMC: 2729318. DOI: 10.1038/nrg2455. View

13.

Desset S, Meignin C, Dastugue B, Vaury C . COM, a heterochromatic locus governing the control of independent endogenous retroviruses from Drosophila melanogaster. Genetics. 2003; 164(2):501-9. PMC: 1462594. DOI: 10.1093/genetics/164.2.501. View

14.

Ambros V, Lee R, Lavanway A, Williams P, Jewell D . MicroRNAs and other tiny endogenous RNAs in C. elegans. Curr Biol. 2003; 13(10):807-18. DOI: 10.1016/s0960-9822(03)00287-2. View

15.

Chawla G, Sokol N . MicroRNAs in Drosophila development. Int Rev Cell Mol Biol. 2011; 286:1-65. DOI: 10.1016/B978-0-12-385859-7.00001-X. View

16.

Wang S, Elgin S . Drosophila Piwi functions downstream of piRNA production mediating a chromatin-based transposon silencing mechanism in female germ line. Proc Natl Acad Sci U S A. 2011; 108(52):21164-9. PMC: 3248523. DOI: 10.1073/pnas.1107892109. View

17.

Brasset E, Taddei A, Arnaud F, Faye B, Fausto A, Mazzini M . Viral particles of the endogenous retrovirus ZAM from Drosophila melanogaster use a pre-existing endosome/exosome pathway for transfer to the oocyte. Retrovirology. 2006; 3:25. PMC: 1524798. DOI: 10.1186/1742-4690-3-25. View

18.

Han J, Lee Y, Yeom K, Nam J, Heo I, Rhee J . Molecular basis for the recognition of primary microRNAs by the Drosha-DGCR8 complex. Cell. 2006; 125(5):887-901. DOI: 10.1016/j.cell.2006.03.043. View

19.

Hamada-Kawaguchi N, Nore B, Kuwada Y, Smith C, Yamamoto D . Btk29A promotes Wnt4 signaling in the niche to terminate germ cell proliferation in Drosophila. Science. 2014; 343(6168):294-7. DOI: 10.1126/science.1244512. View

20.

Ding S, Lu R . Virus-derived siRNAs and piRNAs in immunity and pathogenesis. Curr Opin Virol. 2011; 1(6):533-44. PMC: 3237678. DOI: 10.1016/j.coviro.2011.10.028. View