The piRNA Pathway Guards the Germline Genome Against Transposable Elements

AbstractEpigenetic resetting in germ cells during development leads to the de-repression of transposable elements (TEs). piRNAs protect fetal germ cells from potentially harmful TEs by targeted destruction of mRNA and deposition of repressive epigenetic marks. Here we provide the first evidence for an active piRNA pathway and TE repression in germ cells of human fetal testis. We identify pre-pachytene piRNAs with features of secondary amplification that map most abundantly to L1 family TEs. We find that L1-ORF1p expression is heterogeneous in fetal germ cells, peaks at mid-gestation and declines concomitantly with increasing levels of piRNAs and H3K9me3, as well as nuclear localization of HIWI2. Surprisingly, following this decline, the same cells with accumulation of L1-ORF1p display highest levels of HIWI2 and H3K9me3, whereas L1-ORF1p low cells are also low in HIWI2 and H3K9me3. Conversely, earlier in development, the germ cells lacking L1-ORF1p express high levels of the chaperone HSP90a. We propose that a subset of HSP90a-armed germ cells resists L1 expression, whereas only those vulnerable L1-expressing germ cells activate the PIWI-piRNA repression pathway which leads to epigenetic silencing of L1 via H3K9me3.

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Erratum to: Small RNAs from a Big Genome: The piRNA Pathway and Transposable Elements in the Salamander Species Desmognathus fuscus

Journal of Molecular Evolution ◽

10.1007/s00239-016-9769-1 ◽

2016 ◽

Vol 84 (1) ◽

pp. 67-67

Author(s):

M. J. Madison-Villar ◽

Cheng Sun ◽

Nelson C. Lau ◽

Matthew L. Settles ◽

Rachel Lockridge Mueller

Keyword(s):

Transposable Elements ◽

Small Rnas ◽

Pirna Pathway ◽

Salamander Species

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Nuclear Argonaute Piwi Gene Mutation Affects rRNA by Inducing rRNA Fragment Accumulation, Antisense Expression, and Defective Processing in Drosophila Ovaries

International Journal of Molecular Sciences ◽

10.3390/ijms21031119 ◽

2020 ◽

Vol 21 (3) ◽

pp. 1119

Author(s):

Anastasia D. Stolyarenko

Keyword(s):

Drosophila Melanogaster ◽

Transposable Elements ◽

Gene Mutation ◽

Ribosomal Rna ◽

5S Rrna ◽

Rna Surveillance ◽

5.8S Rrna ◽

Argonaute Family ◽

Main Component ◽

Pirna Pathway

Drosophila key nuclear piRNA silencing pathway protein Piwi of the Argonaute family has been classically studied as a factor controlling transposable elements and fertility. Piwi has been shown to concentrate in the nucleolus for reasons largely unknown. Ribosomal RNA is the main component of the nucleolus. In this work the effect of a piwi mutation on rRNA is described. This work led to three important conclusions: A mutation in piwi induces antisense 5S rRNA expression, a processing defect of 2S rRNA orthologous to the 3′-end of eukaryotic 5.8S rRNA, and accumulation of fragments of all five rRNAs in Drosophila melanogaster ovaries. Hypotheses to explain these phenomena are proposed, possibly involving the interaction of the components of the piRNA pathway with the RNA surveillance machinery.

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Two modes of targeting transposable elements by piRNA pathway in human testis

RNA ◽

10.1261/rna.060939.117 ◽

2017 ◽

Vol 23 (11) ◽

pp. 1614-1625 ◽

Cited By ~ 17

Author(s):

Ildar Gainetdinov ◽

Yulia Skvortsova ◽

Sofia Kondratieva ◽

Sergey Funikov ◽

Tatyana Azhikina

Keyword(s):

Transposable Elements ◽

Human Testis ◽

Pirna Pathway

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Complex Genetic Interactions between Piwi and HP1a in the Repression of Transposable Elements and Tissue-Specific Genes in the Ovarian Germline

International Journal of Molecular Sciences ◽

10.3390/ijms222413430 ◽

2021 ◽

Vol 22 (24) ◽

pp. 13430

Author(s):

Artem A. Ilyin ◽

Anastasia D. Stolyarenko ◽

Nikolay Zenkin ◽

Mikhail S. Klenov

Keyword(s):

Transposable Elements ◽

Rna Seq ◽

Heterochromatin Protein ◽

Protein Coding ◽

Tissue Specific ◽

Small Set ◽

Similar Genetic Background ◽

Genomic Regions ◽

Pirna Pathway ◽

Inappropriate Expression

Insertions of transposable elements (TEs) in eukaryotic genomes are usually associated with repressive chromatin, which spreads to neighbouring genomic sequences. In ovaries of Drosophila melanogaster, the Piwi-piRNA pathway plays a key role in the transcriptional silencing of TEs considered to be exerted mostly through the establishment of H3K9me3 histone marks recruiting Heterochromatin Protein 1a (HP1a). Here, using RNA-seq, we investigated the expression of TEs and the adjacent genomic regions upon Piwi and HP1a germline knockdowns sharing a similar genetic background. We found that the depletion of Piwi and HP1a led to the derepression of only partially overlapping TE sets. Several TEs were silenced predominantly by HP1a, whereas the upregulation of some other TEs was more pronounced upon Piwi knockdown and, surprisingly, was diminished upon a Piwi/HP1a double-knockdown. We revealed that HP1a loss influenced the expression of thousands of protein-coding genes mostly not adjacent to TE insertions and, in particular, downregulated a putative transcriptional factor required for TE activation. Nevertheless, our results indicate that Piwi and HP1a cooperatively exert repressive effects on the transcription of euchromatic loci flanking the insertions of some Piwi-regulated TEs. We suggest that this mechanism controls the silencing of a small set of TE-adjacent tissue-specific genes, preventing their inappropriate expression in ovaries.

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The Drosophila TART transposon manipulates the piRNA pathway as a counter-defense strategy to limit host silencing

10.1101/2020.02.20.957324 ◽

2020 ◽

Author(s):

Christopher E. Ellison ◽

Meenakshi S. Kagda ◽

Weihuan Cao

Keyword(s):

Transposable Elements ◽

Nuclear Export ◽

Critical Role ◽

Host Genome ◽

Factor Gene ◽

Defense Strategy ◽

Pirna Pathway

AbstractCo-evolution between transposable elements (TEs) and their hosts can be antagonistic, where TEs evolve to avoid silencing and the host responds by reestablishing TE suppression, or mutualistic, where TEs are co-opted to benefit their host. The TART-A TE functions as an important component of Drosophila telomeres, but has also reportedly inserted into the D. melanogaster nuclear export factor gene nxf2. We find that, rather than inserting into nxf2, TART-A has actually captured a portion of nxf2 sequence. We show that Nxf2 is involved in suppressing TART-A activity via the piRNA pathway and that TART-A produces abundant piRNAs, some of which are antisense to the nxf2 transcript. We propose that capturing nxf2 sequence allowed TART-A to target the nxf2 gene for piRNA-mediated repression and that these two elements are engaged in antagonistic co-evolution despite the fact that TART-A is serving a critical role for its host genome.

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Pan-arthropod analysis reveals somatic piRNAs as an ancestral defence against transposable elements

10.1101/185694 ◽

2017 ◽

Cited By ~ 1

Author(s):

Samuel H. Lewis ◽

Kaycee A. Quarles ◽

Yujing Yang ◽

Melanie Tanguy ◽

Lise Frézal ◽

...

Keyword(s):

Transposable Elements ◽

Small Rna ◽

Rna Silencing ◽

Individual Species ◽

Rna Molecules ◽

Horseshoe Crabs ◽

Silencing Pathways ◽

Pirna Pathway ◽

Interference Mechanism

AbstractIn animals, small RNA molecules termed PIWI-interacting RNAs (piRNAs) silence transposable elements (TEs), protecting the germline from genomic instability and mutation. piRNAs have been detected in the soma in a few animals, but these are believed to be specific adaptations of individual species. Here, we report that somatic piRNAs were likely present in the ancestral arthropod more than 500 million years ago. Analysis of 20 species across the arthropod phylum suggests that somatic piRNAs targeting TEs and mRNAs are common among arthropods. The presence of an RNA-dependent RNA polymerase in chelicerates (horseshoe crabs, spiders, scorpions) suggests that arthropods originally used a plant-like RNA interference mechanism to silence TEs. Our results call into question the view that the ancestral role of the piRNA pathway was to protect the germline and demonstrate that small RNA silencing pathways have been repurposed for both somatic and germline functions throughout arthropod evolution.

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Adaptive evolution among cytoplasmic piRNA proteins leads to decreased genomic auto-immunity

10.1101/521773 ◽

2019 ◽

Cited By ~ 1

Author(s):

Luyang Wang ◽

Daniel A. Barbash ◽

Erin S. Kelleher

Keyword(s):

Immune System ◽

Transposable Elements ◽

Adaptive Evolution ◽

Small Rna ◽

Functional Divergence ◽

Harmful Effect ◽

Effector Proteins ◽

Host Cells ◽

Selfish Dna ◽

Pirna Pathway

AbstractIn metazoan germlines, the piRNA pathway acts as a genomic immune system, employing small RNA-mediated silencing to defend host DNA from the harmful effects of transposable elements (TEs). In response to dynamic changes in TE content, host genomes are proposed to alter the piRNAs that they produce in order to silence the most active TE families. Surprisingly, however, piRNA pathway proteins, which execute piRNA biogenesis and enforce silencing of targeted sequences, also evolve rapidly and adaptively in animals. If TE silencing evolves through changes in piRNAs, what necessitates changes in piRNA pathway proteins? Here we used interspecific complementation to test for functional differences between Drosophila melanogaster and D. simulans alleles of three adaptively evolving piRNA pathway proteins: Armitage, Aubergine and Spindle-E. Surprisingly, we observed interspecific divergence in the regulation of only a handful of TE families, which were more robustly silenced by the heterospecific piRNA pathway protein. This suggests that positive selection does not act on piRNA effector proteins to enhance their function in TE repression, but rather that TEs may evolve to “escape” silencing by homospecific alleles. We also discovered that D. simulans alleles of aub and armi exhibit enhanced off-target effects on host transcripts in a D. melanogaster background, suggesting the avoidance of genomic auto-immunity as a critical target of selection. Our observations suggest that piRNA effector proteins are subject to an evolutionary trade-off between defending the host genome from the harmful effect of TEs while also minimizing friendly fire against host genes.Author SummaryTransposable elements are mobile fragments of selfish DNA that burden host genomes with deleterious mutations and incite genome instability. Host cells employ a specialized small-RNA mediated silencing pathway, the piRNA pathway, to act as a genomic immune system suppressing the mobilization of TEs. Changes in genomic TE content are met with rapid changes in the piRNA pool, thereby maintain host control over transposition. However, piRNA pathway proteins—which enact piRNA biogenesis and silence target TEs—also evolve adaptively. To isolate forces that underlie this adaptive evolution, we examined functional divergence between two Drosophila species for three adaptively evolving piRNA pathway proteins. To our surprise, we found very few differences in TE regulation, suggesting that evolution has not generally acted to enhance control of TE parasites. Rather, we discovered interspecific differences in the regulation of host mRNAs for two proteins, which suggested that proteins evolve to avoid off-target silencing of host transcripts. We propose that the avoidance of such “genomic autoimmunity” is an important and underappreciated force driving the adaptive evolution of piRNA proteins.

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