Discrete Small RNA-Generating Loci as Master Regulators of Transposon Activity in Drosophila
Open accessAbstract
Drosophila Piwi-family proteins have been implicated in transposon control. Here, we examine piwi-interacting RNAs (piRNAs) associated with each Drosophila Piwi protein and find that Piwi and Aubergine bind RNAs that are predominantly antisense to transposons, whereas Ago3 complexes contain predominantly sense piRNAs. As in mammals, the majority of Drosophila piRNAs are derived from discrete genomic loci. These loci comprise mainly defective transposon sequences, and some have previously been identified as master regulators of transposon activity. Our data suggest that heterochromatic piRNA loci interact with potentially active, euchromatic transposons to form an adaptive system for transposon control. Complementary relationships between sense and antisense piRNA populations suggest an amplification loop wherein each piRNA-directed cleavage event generates the 5' end of a new piRNA. Thus, sense piRNAs, formed following cleavage of transposon mRNAs may enhance production of antisense piRNAs, complementary to active elements, by directing cleavage of transcripts from master control loci.
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Transposable element transcripts are targets of a conserved piRNA pathway that binds to them and mediates their degradation.
“In addition, transposable element transcripts are the targets of a well-conserved pathway involving piRNAs, small regulatory RNAs that bind to transposable element transcripts and mediate their degradation3.”
From Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies (2018) · cites this paper as [3]
Flamenco is known to encode a major piRNA cluster.
“Since flamenco is known to encode a major piRNA cluster3,26, and piRNAs have recently been reported to be differentially expressed in the human Alzheimer’s disease brain27,28, we next determined if piRNAs are involved in dysfunctional transposable element control in the tauopathy brain.”
From Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies (2018) · cites this paper as [3]
Cells have two layers of defense against potentially deleterious transposable element activation: transcription is limited by heterochromatin-mediated silencing, and transcripts are cleared by piRNA-mediated degradation.
“Based on current understanding, cells have two layers of defense against potentially deleterious transposable element activation: 1) Transposable element transcription is limited by heterochromatin-mediated silencing, and 2) Transposable element transcripts are cleared from the cell by piRNA-mediated degradation”
From Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies (2018) · cites this paper as [3]
Piwi and piRNAs are most abundant in the germline, where they play a key role in retrotransposon silencing at the RNA and chromatin levels.
“Piwi and piRNAs are most abundant in the germline, where they play a key role in retrotransposon silencing at the RNA and chromatin levels”
From The Role of Retrotransposons and Endogenous Retroviruses in Age-Dependent Neurodegenerative Disorders (2024) · cites this paper as Brennecke et al. 2007
Cites
Sarot, E., Payen-Groschêne, G., Bucheton, A., & Pélisson, A. (2004) · Genetics · doi:10.1534/genetics.166.3.1313 · Cited by 251 · see citing works
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The Piwi-piRNA Pathway Provides an Adaptive Defense in the Transposon Arms Race
Aravin, A. A., Hannon, G. J., & Brennecke, J. (2007) · Science · doi:10.1126/science.1146484 · Cited by 1,096 · see citing works
Self-citationMolecular Signals of Epigenetic States
Bonasio, R., Tu, S., & Reinberg, D. (2010) · Science · doi:10.1126/science.1191078 · Cited by 912 · see citing works
piRNAs Can Trigger a Multigenerational Epigenetic Memory in the Germline of C. elegans
Ashe, A., Sapetschnig, A., Weick, E.-M., Mitchell, J., Bagijn, M. P., Cording, A. C., Doebley, A.-L., Goldstein, L. D., Lehrbach, N. J., Le Pen, J., et al. (2012) · Cell · doi:10.1016/j.cell.2012.06.018 · Cited by 754 · see citing works
Non-coding RNAs as regulators of gene expression and epigenetics
Kaikkonen, M. U., Lam, M. T. Y., & Glass, C. K. (2011) · Cardiovascular Research · doi:10.1093/cvr/cvr097 · Cited by 764 · see citing works
Tau promotes neurodegeneration through global chromatin relaxation
Frost, B., Hemberg, M., Lewis, J., & Feany, M. B. (2014) · Nature Neuroscience · doi:10.1038/nn.3639 · Cited by 519 · see citing works
“Ago3 regulates PIWI-associated RNAs (piRNAs) 32 , a highly conserved class of small RNAs that are required for post-transcriptional gene silencing of transposons 33,34 .”
Annotating non-coding regions of the genome.
Alexander, R. P., Fang, G., Rozowsky, J., Snyder, M., & Gerstein, M. B. (2010) · Nature Reviews Genetics · doi:10.1038/nrg2814 · Cited by 464 · see citing works
Life of RISC: Formation, action, and degradation of RNA-induced silencing complex
Iwakawa, H.-O., & Tomari, Y. (2022) · Molecular Cell · doi:10.1016/j.molcel.2021.11.026 · Cited by 488 · see citing works
Juliano, C., Wang, J., & Lin, H. (2011) · Annual Review of Genetics · doi:10.1146/annurev-genet-110410-132541 · Cited by 374 · see citing works
<i>Drosophila</i> PIWI associates with chromatin and interacts directly with HP1a
Brower-Toland, B., Findley, S. D., Jiang, L., Liu, L., Yin, H., Dus, M., Zhou, P., Elgin, S. C. R., & Lin, H. (2007) · Genes & Development · doi:10.1101/gad.1564307 · Cited by 350 · see citing works
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From guide to target: molecular insights into eukaryotic RNA-interference machinery
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A heterochromatin-dependent transcription machinery drives piRNA expression
Andersen, P. R., Tirian, L., Vunjak, M., & Brennecke, J. (2017) · Nature · doi:10.1038/nature23482 · Cited by 280 · see citing works
Self-citationCzech, B., Preall, J. B., McGinn, J., & Hannon, G. J. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.04.007 · Cited by 269 · see citing works
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Szyf, M. (2015) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2014.12.004 · Cited by 238 · see citing works
Functional involvement of Tudor and dPRMT5 in the piRNA processing pathway in Drosophila germlines
Nishida, K. M., Okada, T. N., Kawamura, T., Mituyama, T., Kawamura, Y., Inagaki, S., Huang, H., Chen, D., Kodama, T., Siomi, H., et al. (2009) · The EMBO Journal · doi:10.1038/emboj.2009.365 · Cited by 197 · see citing works
Silencio/CG9754 connects the Piwi-piRNA complex to the cellular heterochromatin machinery
Sienski, G., Batki, J., Senti, K.-A., Dönertas, D., Tirian, L., Meixner, K., & Brennecke, J. (2015) · Genes & Development · doi:10.1101/gad.271908.115 · Cited by 185 · see citing works
Self-citationpiRNA-mediated transgenerational inheritance of an acquired trait
Grentzinger, T., Armenise, C., Brun, C., Mugat, B., Serrano, V., Pelisson, A., & Chambeyron, S. (2012) · Genome Research · doi:10.1101/gr.136614.111 · Cited by 162 · see citing works
A somatic piRNA pathway in the Drosophila fat body ensures metabolic homeostasis and normal lifespan
Jones, B. C., Wood, J. G., Chang, C., Tam, A. D., Franklin, M. J., Siegel, E. R., & Helfand, S. L. (2016) · Nature Communications · doi:10.1038/ncomms13856 · Cited by 130 · see citing works
Connecting the dots between tau dysfunction and neurodegeneration
Frost, B., Götz, J., & Feany, M. B. (2015) · Trends in Cell Biology · doi:10.1016/j.tcb.2014.07.005 · Cited by 124 · see citing works
Transcriptome-wide piRNA profiling in human brains of Alzheimer's disease
Qiu, W., Guo, X., Lin, X., Yang, Q., Zhang, W., Zhang, Y., Zuo, L., Zhu, Y., Li, C.-S. R., Ma, C., et al. (2017) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2017.05.020 · Cited by 105 · see citing works
Frost, B., & Dubnau, J. (2024) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-082823-020615 · Cited by 45 · see citing works
Binding of SU(VAR)3-9 partially depends on SETDB1 in the chromosomes of drosophila melanogaster
Maksimov, D. A., & Koryakov, D. E. (2019) · Cells · doi:10.3390/cells8091030 · Cited by 8 · see citing works
RG motifs promote piRNA-mediated gene silencing in <i>C. elegans</i>
Wallis, D. C., & Phillips, C. M. (2025) · Nucleic Acids Research · doi:10.1093/nar/gkaf1331 · Cited by 3 · see citing works
- Authors
- Brennecke, J., Aravin, A. A., Stark, A., Dus, M., Kellis, M., Sachidanandam, R., & Hannon, G. J.
- Affiliations
- Howard Hughes Medical Institute (US)
- Broad Institute (US)
- Corresponding author
- Hannon, Gregory J.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2007-03
- Volume
- 128
- Issue
- 6
- Pages
- 1089-1103
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W1976342457
- Cited by
- 2,524
- References
- 1
- Citations by year
- 2026: 78 · 2025: 124 · 2024: 110 · 2023: 107 · 2022: 124 · 2021: 159 · 2020: 125 · 2019: 151 · 2018: 140 · 2017: 129 · 2016: 114 · 2015: 139 · 2014: 155 · 2013: 154 · 2012: 144
- FWCI
- 167.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- piRNA, transposon silencing, PIWI proteins, eggplant, AGO3, heterochromatin, Drosophila
- MeSH terms
- Animals, Base Sequence, DNA Transposable Elements, Drosophila melanogaster, Female, Multigene Family, Male, Molecular Sequence Data, Ovary, Peptide Initiation Factors, Proteins, Recombinant Proteins, RNA, Transcription Factors, RNA, Antisense, RNA-Binding Proteins, Retroelements, Drosophila Proteins, RNA-Induced Silencing Complex, Genome, Insect, Argonaute Proteins
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