Abstract—Regulation of retrotransposon activity in somatic tissues is a complex mechanism that has still not been studied in detail. It is strongly believed that siRNA interference is main mechanism of retrotransposon activity regulation outside the gonads, but recently was demonstrated that piRNA interference participates in retrotransposon repression during somatic tissue development. In this work, using RT-PCR, we demonstrated that during ontogenesis piRNA interference determinates retrotransposon expression level on imago stage and retrotransposons demonstrate tissue-specific expression. The major factor of retrotransposon tissue-specific expression is presence of transcription factor binding sites in their regulatory regions.
REFERENCES
Théron E., Dennis C., Brasset E., Vaury C. 2014. Distinct features of the piRNA pathway in somatic and germ cells: From piRNA cluster transcription to piRNA processing and amplification. Mobile DNA. 5, 28.
Qi H., Watanabe T., Ku H.-Y., Liu N., Zhong M., Lin H. 2011. The Yb Body, a major site for Piwi-associated RNA biogenesis and a gateway for Piwi expression and transport to the nucleus in somatic cells. Biol. Chem. 286, 3789–3797. https://doi.org/10.1074/jbc.M110.193888
Dumesic P.A., Natarajan P., Chen C., Drinnenberg I.A., Schiller B.J., Thompson J., Moresco J.J., Yates J.R., Bartel D.P., Madhani H.D. 2013. Stalled spliceosomes are a signal for RNAi-mediated genome defense. Cell. 152, 957–968. https://doi.org/10.1016/j.cell.2013.01.046
Zhang Z., Wang J., Schultz N., Zhang F., Parhad S.S., Tu S., Vreven T., Zamore P.D., Weng Z., Theurkauf W.E. 2014. The HP1 homolog rhino anchors a nuclear complex that suppresses piRNA precursor splicing. Cell. 157, 1353–1363. https://doi.org/10.1016/j.cell.2014.04.030
Wakisaka K.T., Tanaka R., Hirashima T., Muraoka Y., Azuma Y., Yoshida H., Ichiyanagi K., Ohno S., Itoh M., Yamaguchi M. 2019. Novel roles of Drosophila FUS and Aub responsible for piRNA biogenesis in neuronal disorders. 1708, 207‒219. https://doi.org/10.1016/j.brainres.2018.12.028
Andersen P.R., Tirian L., Vunjak M., Brennecke J. 2017. A heterochromatin-dependent transcription machinery drives piRNA expression. Nature. 549, 54–59. https://doi.org/10.1038/nature23482
Schnabl J., Wang J., Hohmann U., Gehre M., Batki J., Andreev V.I., Purkhauser K., Fasching N., Duchek P., Novatchkova M., Mechtler K., Plaschka C., Patel D.J., Brennecke J. 2021. Molecular principles of Piwi-mediated cotranscriptional silencing through the dimeric SFiNX complex. Genes Dev. 35, 392–409. https://doi.org/10.1101/gad.347989.120
Chang Y.-H., Dubnau J. 2019. The gypsy endogenous retrovirus drives non-cell-autonomous propagation in a Drosophila tdp-43 model of neurodegeneration. Curr. Biol. 29, 3135‒3152.e4. https://doi.org/10.1016/j.cub.2019.07.071
Onishi R., Sato K., Murano K., Negishi L., Siomi H., Siomi M.C. 2020. Piwi suppresses transcription of Brahma-dependent transposons via Maelstrom in ovarian somatic cells. Sci. Adv. 6 (50), eaaz 7420. https://doi.org/10.1126/sciadv.aaz7420
Muerdter F., Guzzardo P.M., Gillis J., Luo Y., Yu Y., Chen C., Fekete R., Hannon G.J. 2013. A genome-wide RNAi screen draws a genetic framework for transposon control and primary piRNA biogenesis in Drosophila. Mol. Cell. 50, 736–748. https://doi.org/10.1016/j.molcel.2013.04.006
Stolyarenko A.D. 2020. Nuclear argonaute Piwi gene mutation affects rRNA by inducing rRNA fragment accumulation, antisense expression, and defective processing in Drosophila ovaries. Int. J. Mol. Sci. 21, 1119. https://doi.org/10.3390/ijms21031119
Kim K.W. 2019. PIWI proteins and piRNAs in the nervous system. Mol. Cells. 42, 12, 828‒835. https://doi.org/10.14348/molcells.2019.0241
Kim K.W., Tang N.H., Andrusiak M.G., Wu Z., Chisholm A.D., ** Y. 2018. A neuronal piRNA pathway inhibits axon regeneration in C. elegans. Neuron. 97, 511‒519.e6. https://doi.org/10.1016/j.neuron.2018.01.014
Perrat P.N., DasGupta S., Wang J., Theurkauf W., Weng Z., Rosbash M., Waddell S. 2013. Transposition-driven genomic heterogeneity in the Drosophila brain. Science. 340, 91–95. https://doi.org/10.1126/science.1231965
Ross R.J., Weiner M.M., Lin H. 2014. PIWI proteins and PIWI-interacting RNAs in the soma. Nature. 505, 353–359. https://doi.org/10.1038/nature12987
Zuo L., Wang Z., Tan Y., Chen X., Luo X. 2016. pi-RNAs and their functions in the brain. Int. J. Hum. Genet. 16 (1–2), 53–60. https://doi.org/10.1080/09723757.2016.11886278
Nampoothiri S.S., Rajanikant G.K. 2017. Decoding the ubiquitous role of microRNAs in neurogenesis. Mol. Neurobiol. 54, 2003–2011. https://doi.org/10.1007/s12035-016-9797-2
Trizzino M., Kapusta A., Brown C.D. 2018. Transposable elements generate regulatory novelty in a tissue-specific fashion. BMC Genomics. 19, 468. https://doi.org/10.1186/s12864-018-4850-3
Moschetti R., Palazzo A., Lorusso P., Viggiano L., Massimiliano Marsano R. 2020. “What You Need, Baby, I Got It”: Transposable elements as suppliers of cis-operating sequences in Drosophila. Biology (Basel). 9, 25. https://doi.org/10.3390/biology9020025
Mustafin R.N., Khusnutdinova E.K. 2020. Involvement of transposable elements in neurogenesis. Vavilov J. Genet. Breed. 24, 209–218. https://doi.org/10.18699/VJ20.613
Villanueva-Cañas J.L., Horvath V., Aguilera L., González J. 2019. Diverse families of transposable elements affect the transcriptional regulation of stress-response genes in Drosophila melanogaster. Nucleic Acids Res. 47 (13), 6842‒6857. https://doi.org/10.1093/nar/gkz490
Senft A.D., Macfarlan T.S. 2021. Transposable elements shape the evolution of mammalian development. Nat. Rev. Genet. 22 (11), 691‒711. https://doi.org/10.1038/s41576-021-00385-1
Kim A.I., Belyaeva E.S., Larkina Z.G., Aslanyan M.M. 1989. Genetic instability and transposition of the mobile element MDG4 in the Drosophila melanogaster mutator line. Russ. J. Genet. 25 (10), 1747–1756.
Hafer N., Schedl P. 2006. Dissection of larval CNS in Drosophila melanogaster. J. Vis. Exp. 1, 85. https://doi.org/10.3791/85-v
Hur J.K., Luo Y., Moon S., Ninova M., Marinov G.K., Chung Y.D., Aravin A.A. 2016. Splicing-independent loading of TREX on nascent RNA is required for efficient expression of dual-strand piRNA clusters in Drosophila. Genes Dev. 30, 840–855. https://doi.org/10.1101/gad.276030.115
Sayers E.W., Bolton E.E., Brister J.R., Canese K., Chan J., Comeau D.C., Connor R., Funk K., Kelly C., Kim S., Madej T., Marchler-Bauer A., Lanczycki C., Lathrop S., Lu Z., Thibaud-Nissen F., Murphy T., Phan L., Skripchenko Y., Tse T., Wang J., Williams R., Trawick B.W., Pruitt K.D., Sherry S.T. 2022. Database resources of the national center for biotechnology information. Nucleic Acids Res. 50 (D1), D20‒D26. https://doi.org/10.1093/nar/gkab1112
Nefedova L.N., Urusov F.A., Romanova N.I., Shmel’kova A.O., Kim A.I. 2012. Study of the transcriptional and transpositional activities of the tirant retrotransposon in Drosophila melanogaster strains mutant for the flamenco locus. Russ. J. Genet. 48, 1089–1096. https://doi.org/10.1134/S1022795412110063
Robinson J.T., Thorvaldsdóttir H., Winckler W., Guttman M., Lander E.S., Getz G., Mesirov J.P. 2011. Integrative genomics viewer. Nat. Biotechnol. 29 (1), 24‒26. https://doi.org/10.1038/nbt.1754
Ewing A.D., Smits N., Sanchez-Luque F.J., Faivre J., Brennan P.M., Richardson S.R., Cheetham S.W., Faulkner G.J. 2020. Nanopore sequencing enables comprehensive transposable element epigenomic profiling. Mol. Cell. 80, 915‒928.e5. https://doi.org/10.1016/j.molcel.2020.10.024
Kaminker J.S., Bergman C.M., Kronmiller B., Carlson J., Svirskas R., Patel S., Frise E., Whe-eler D.A., Lewis S.E., Rubin G.M., Ashburner M., Celniker S.E. 2002. The transposable elements of the Drosophila melanogaster euchromatin: A genomics perspective. Genome Biol. 3 (12), RESEARCH0084. https://doi.org/10.1186/gb-2002-3-12-research0084
Okonechnikov K., Golosova O., Fursov M., Unipro 2012. UGENE: A unified bioinformatics toolkit. Bioinformatics. 28, 1166‒1167. https://doi.org/10.1093/bioinformatics/bts091
Gramates L.S., Agapite J., Attrill H., Calvi B.R., Crosby M.A., Dos Santos G., Goodman J.L., Goutte-Gattat D., Jenkins V.K., Kaufman T., Larkin A., Matthews B.B., Millburn G., Strelets V.B., the FlyBase Consortium. 2022. FlyBase: A guided tour of highlighted features. Genetics. 220 (4), iyac035. https://doi.org/10.1093/genetics/iyac035
Lee Ch., Huang Ch.-Hs. 2013. LASAGNA-Search: An integrated web tool for transcription factor binding site search and visualization. BioTechniques. 54, 141–153. https://doi.org/doi 10.2144/000113999
Mani S.R., Megosh H., Lin H. 2014. PIWI proteins are essential for early Drosophila embryogenesis. Develop. Biol. 385, 340–349. https://doi.org/10.1016/j.ydbio.2013.10.017
Romero-Soriano V., Guerreiro M.P.G. 2016. Expression of the retrotransposon helena reveals a complex pattern of TE deregulation in Drosophila hybrids. PLoS One. 11, e0147903. https://doi.org/10.1371/journal.pone.0147903
Wang S.H., Elgin S.C. 2011. 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. 108 (52), 21164‒21169. https://doi.org/10.1073/pnas.1107892109
Klenov M.S., Sokolova O.A., Yakushev E.Y., Stolyarenko A.D., Mikhaleva E.A., Lavrov S.A., Gvozdev V.A. 2011. Separation of stem cell maintenance and transposon silencing functions of Piwi protein. Proc. Natl. Acad. Sci. U. S. A. 108 (46), 18760‒18765. https://doi.org/10.1073/pnas.1106676108
Gebert D., Neubert L.K., Lloyd C., Gui J., Lehmann R., Teixeira F.K. 2021. Large Drosophila ge-rmline piRNA clusters are evolutionarily labile and dispensable for transposon regulation. Mol. Cell. 81 (19), 3965‒3978.e5. https://doi.org/10.1016/j.molcel.2021.07.011
Chung W.-J., Okamura K., Martin R., Lai E.C. 2008. Endogenous RNA interference provides a somatic defense against drosophila transposons. Curr. Biol. 18, 795–802. https://doi.org/10.1016/j.cub.2008.05.006
Carthew R.W., Sontheimer E.J. 2009. Origins and mechanisms of miRNAs and siRNAs. Cell. 136, 642–655. https://doi.org/10.1016/j.cell.2009.01.035
Cacchione S., Cenci G., Raffa G.D. 2020. Silence at the end: How drosophila regulates expression and transposition of telomeric retroelements. J. Mol. Biol. 432, 4305–4321. https://doi.org/10.1016/j.jmb.2020.06.004
Palazzo A., Lorusso P., Miskey C., Walisko O., Gerbino A., Marobbio C.M.T., Ivics Z., Marsano R.M. 2019. Transcriptionally promiscuous “Blurry” promoters in Tc1/mariner transposons allow transcription in distantly related genomes. Mobile DNA. 10, 13. https://doi.org/10.1186/s13100-019-0155-6
Funding
This research was funded by the Russian Science Foundation, grant number 22-24-00305.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
CONFLICT OF INTEREST
The authors of this work declare that they have no conflicts of interest.
ETHICS APPROVAL AND CONSENT TO PARTICIPATE
This work does not contain any studies involving human and animal subjects.
Additional information
Publisher’s Note.
Pleiades Publishing remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Milyaeva, P.A., Kukushkina, I.V., Lavrenov, A.R. et al. Regulation of Retrotransposons in Drosophila melanogaster Somatic Tissues. Mol Biol 58, 81–101 (2024). https://doi.org/10.1134/S0026893324010096
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S0026893324010096