scholarly journals Part 1: The PIWI-piRNA Pathway Is an Immune-Like Surveillance Process That Controls Genome Integrity by Silencing Transposable Elements

2020 ◽  
Author(s):  
Didier Meseure ◽  
Kinan Drak Alsibai
Keyword(s):  
Transposable Elements ◽  
Genome Integrity ◽  
Pirna Pathway

scholarly journals yama, a mutant allele of Mov10l1, disrupts retrotransposon silencing and piRNA biogenesis

2020 ◽  
Author(s):  
Yongjuan Guan ◽  
Devanshi Jain ◽  
Scott Keeney ◽  
P. Jeremy Wang
Keyword(s):  
Transposable Elements ◽  
Germ Cell ◽  
Rna Helicase ◽  
Cell Development ◽  
Terminal Region ◽  
Single Amino Acid ◽  
Genome Integrity ◽  
Wild Type ◽  
Germ Cell Development ◽  
Pirna Pathway

AbstractPiwi-interacting RNAs (piRNAs) play critical roles in protecting germline genome integrity and promoting normal spermiogenic differentiation. In mammals, there are two populations of piRNAs: pre-pachytene and pachytene piRNAs. Transposon-rich pre-pachytene piRNAs are expressed in fetal and perinatal germ cells and are required for retrotransposon silencing, whereas transposon-poor pachytene piRNAs are expressed in spermatocytes and round spermatids and regulate mRNA transcript levels. MOV10L1, a germ cell-specific RNA helicase, is essential for the production of both populations of piRNAs. Although the requirement of the RNA helicase domain located in the MOV10L1 C-terminal region for piRNA biogenesis is well known, its large N-terminal region remains mysterious. Here we report a novel Mov10l1 mutation in the Mov10l1 N-terminal region named yama. The yama mutation results in a single amino acid substitution V229E. The yama mutation causes meiotic arrest, de-repression of transposable elements, and male sterility because of defects in pre-pachytene piRNA biogenesis. Moreover, restricting the Mov10l1 mutation effects to later stages in germ cell development by combining with a postnatal conditional deletion of a complementing wild-type allele causes absence of pachytene piRNAs, accumulation of piRNA precursors, polar conglomeration of piRNA pathway proteins in spermatocytes, and spermiogenic arrest. Mechanistically, the V229E substitution in MOV10L1 reduces its interaction with PLD6, an endonuclease that generates the 5′ ends of piRNA intermediates. Our results uncover an important role for the MOV10L1-PLD6 interaction in piRNA biogenesis throughout male germ cell development.Author SummarySmall non-coding RNAs play critical roles in silencing of exogenous viruses, endogenous retroviruses, and transposable elements, and also play multifaceted roles in controlling gene expression. Piwi-interacting RNAs (piRNAs) are found in gonads in diverse species from flies to humans. An evolutionarily conserved function of piRNAs is to silence transposable elements through an adaptive mechanism and thus to protect the germline genome integrity. In mammals, piRNAs also provide a poorly understood function to regulate postmeiotic differentiation of spermatids. More than two dozen proteins are involved in the piRNA pathway. MOV10L1, a germ-cell-specific RNA helicase, binds to piRNA precursors to initiate piRNA biogenesis. Here we have identified a single amino acid substitution (V229E) in MOV10L1 in the yama mutant. When constitutively expressed as the only source of MOV10L1 throughout germ cell development, the yama mutation abolishes piRNA biogenesis, de-silences transposable elements, and causes meiotic arrest. When the mutant phenotype is instead revealed only later in germ cell development by conditionally inactivating a complementing wild-type copy of the gene, the point mutant abolishes formation of later classes of piRNAs and again disrupts germ cell development. Point mutations in MOV10L1 may thus contribute to male infertility in humans.

scholarly journals Hypomethylated poplars show higher tolerance to water deficit and highlight a dual role for DNA methylation in shoot meristem: regulation of stress response and genome integrity

2020 ◽  
Author(s):  
M.D. Sow ◽  
A-L. Le Gac ◽  
R. Fichot ◽  
S. Lanciano ◽  
A. Delaunay ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Stress Response ◽  
Transposable Elements ◽  
Water Deficit ◽  
Shoot Apical Meristem ◽  
Apical Meristem ◽  
Shoot Meristem ◽  
Genome Integrity ◽  
Dependent Manner ◽  
Altered Expression

AbstractAs fixed and long living organisms subjected to repeated environmental stresses, trees have developed mechanisms such as phenotypic plasticity that help them to cope with fluctuating environmental conditions. Here, we tested the role DNA methylation as a hub of integration, linking plasticity and physiological response to water deficit in the shoot apical meristem of the model tree poplar (Populus). Using a reverse genetic approach, we compared hypomethylated RNAi-ddm1 lines to wild-type trees for drought tolerance. An integrative analysis was realized with phytohormone balance, methylomes, transcriptomes and mobilomes.Hypomethylated lines were more tolerant when subjected to moderate water deficit and were intrinsically more tolerant to drought-induced cavitation. The alteration of the DDM1 machinery induced variation in DNA methylation in a cytosine context dependent manner, both in genes and transposable elements. Hypomethylated lines subjected to water deficit showed altered expression of genes involved in phytohormone pathways, such as salicylic acid and modified hormonal balance. Several transposable elements showed stress- and/or line-specific patterns of reactivation, and we could detect copy number variations for two of them in stressed ddm1 lines.Overall, our data highlight two major roles for DNA methylation in the shoot apical meristem: control of stress response and plasticity through transduction of hormone signaling and maintenance of genome integrity through the control of transposable elements.

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

2016 ◽  
Vol 83 (3-4) ◽  
pp. 126-136 ◽  
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

scholarly journals The nascent RNA binding complex SFiNX licenses piRNA-guided heterochromatin formation

2019 ◽  
Author(s):  
Julia Batki ◽  
Jakob Schnabl ◽  
Juncheng Wang ◽  
Dominik Handler ◽  
Veselin I. Andreev ◽  
...  
Keyword(s):  
Nuclear Export ◽  
Rna Binding ◽  
Transcriptional Silencing ◽  
Genome Integrity ◽  
Rna Transport ◽  
Heterochromatin Formation ◽  
Genome Defense ◽  
Molecular Events ◽  
Pirna Pathway ◽  
Transport Receptor

ABSTRACTThe PIWI-interacting RNA (piRNA) pathway protects animal genome integrity in part through establishing repressive heterochromatin at transposon loci. Silencing requires piRNA-guided targeting of nuclear PIWI proteins to nascent transposon transcripts, yet the subsequent molecular events are not understood. Here, we identify SFiNX (Silencing Factor interacting Nuclear eXport variant), an interdependent protein complex required for Piwi-mediated co-transcriptional silencing in Drosophila. SFiNX consists of Nxf2-Nxt1, a gonad-specific variant of the heterodimeric mRNA export receptor Nxf1-Nxt1, and the Piwi-associated protein Panoramix. SFiNX mutant flies are sterile and exhibit transposon de-repression because piRNA-loaded Piwi is unable to establish heterochromatin. Within SFiNX, Panoramix recruits the heterochromatin effectors, while the RNA binding Nxf2 protein licenses co-transcriptional silencing. Our data reveal how Nxf2 evolved from an RNA transport receptor into a co-transcriptional silencing factor. Thus, NXF-variants, which are abundant in metazoans, can have diverse molecular functions and might have been co-opted for host genome defense more broadly.

scholarly journals The PIWI/piRNA response is relaxed in a rodent that lacks mobilizing transposable elements

2019 ◽  
Author(s):  
Michael W. Vandewege ◽  
Roy N. Patt ◽  
Dana K. Merriman ◽  
David A. Ray ◽  
Federico G. Hoffmann
Keyword(s):  
Transposable Elements ◽  
Ground Squirrel ◽  
Small Rnas ◽  
Oryctolagus Cuniculus ◽  
Genome Integrity ◽  
European Rabbit ◽  
Present Evidence ◽  
Major Threat ◽  
Crucial Difference ◽  
Mammalian Genomes

AbstractTransposable elements (TEs) have the capability to propagate throughout genomes. Mammalian genomes are typically dominated by LINE retrotransposons and their associated SINEs, and their mobilization in the germline is a challenge to genome integrity. There are genomic defenses against TE proliferation and the PIWI/piRNAs defense is among the most well understood. However, the PIWI/piRNA system has been investigated largely in animals with abundant and actively mobilizing TEs and it is unclear how the PIWI/piRNA system functions in the absence of mobilizing TEs. The thirteen-lined ground squirrel provides an excellent opportunity to examine PIWI/piRNA and TE dynamics within the context of minimal, and possibly nonexistent, TE accumulation. We sequenced RNA and small RNAs pools from the testis of juvenile and adult squirrels and compared results to TE and PIWI/piRNA dynamics in the European rabbit (Oryctolagus cuniculus) and house mouse (Mus musculus). Interestingly in squirrels, despite a lack of young insertions, TEs were still actively transcribed in comparable levels to mouse and rabbit. All three PIWI proteins were either not expressed, or only minimally expressed, prior to P8 in squirrel testis, moreover we also discovered that PIWIL4 is expressed all the way into adulthood in the squirrel. This is a crucial difference as PIWIL4 is understood to facilitate TE methylation. We present evidence the PIWI/piRNA system reduced TE expression in rabbit and mouse, but the squirrel PIWIs largely did not affect TE expression. These observations indicate that L1s do not represent a major threat to genome integrity in the squirrel genome, and therefore repression mechanisms have relaxed.

scholarly journals Heterogeneity of transposon expression and activation of the repressive network in human fetal germ cells

2018 ◽  
Author(s):  
Boris Reznik ◽  
Steven A. Cincotta ◽  
Rebecca G. Jaszczak ◽  
Leslie J. Mateo ◽  
Joel Shen ◽  
...  
Keyword(s):  
Transposable Elements ◽  
Nuclear Localization ◽  
Germ Cells ◽  
Epigenetic Silencing ◽  
Epigenetic Marks ◽  
Fetal Testis ◽  
Pirna Pathway

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.

scholarly journals Dimerisation of the PICTS complex via LC8/Cut-up drives co-transcriptional transposon silencing in Drosophila

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Evelyn L Eastwood ◽  
Kayla A Jara ◽  
Susanne Bornelöv ◽  
Marzia Munafò ◽  
Vasileios Frantzis ◽  
...  
Keyword(s):  
Genome Integrity ◽  
Transcriptional Gene Silencing ◽  
Dynein Light Chain ◽  
Heterochromatin Formation ◽  
Transposon Silencing ◽  
Cellular Machinery ◽  
Transposon Insertions ◽  
Pirna Pathway ◽  
Fundamental Requirement ◽  
Rna And Dna

In animal gonads, the PIWI-interacting RNA (piRNA) pathway guards genome integrity in part through the co-transcriptional gene silencing of transposon insertions. In Drosophila ovaries, piRNA-loaded Piwi detects nascent transposon transcripts and instructs heterochromatin formation through the Panoramix-induced co-transcriptional silencing (PICTS) complex, containing Panoramix, Nxf2 and Nxt1. Here, we report that the highly conserved dynein light chain LC8/Cut-up (Ctp) is an essential component of the PICTS complex. Loss of Ctp results in transposon de-repression and a reduction in repressive chromatin marks specifically at transposon loci. In turn, Ctp can enforce transcriptional silencing when artificially recruited to RNA and DNA reporters. We show that Ctp drives dimerisation of the PICTS complex through its interaction with conserved motifs within Panoramix. Artificial dimerisation of Panoramix bypasses the necessity for its interaction with Ctp, demonstrating that conscription of a protein from a ubiquitous cellular machinery has fulfilled a fundamental requirement for a transposon silencing complex.

scholarly journals Mitochondria Associated Germinal Structures in Spermatogenesis: piRNA Pathway Regulation and Beyond

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 399 ◽  
Author(s):  
Xiaoli Wang ◽  
Chunyu Lv ◽  
Ying Guo ◽  
Shuiqiao Yuan
Keyword(s):  
Mrna Translation ◽  
Male Reproduction ◽  
Genome Integrity ◽  
Spermatogenic Cells ◽  
Structural Components ◽  
Chromatoid Body ◽  
Transposon Silencing ◽  
Complex Functions ◽  
Pathway Regulation ◽  
Pirna Pathway

Multiple specific granular structures are present in the cytoplasm of germ cells, termed nuage, which are electron-dense, non-membranous, close to mitochondria and/or nuclei, variant size yielding to different compartments harboring different components, including intermitochondrial cement (IMC), piP-body, and chromatoid body (CB). Since mitochondria exhibit different morphology and topographical arrangements to accommodate specific needs during spermatogenesis, the distribution of mitochondria-associated nuage is also dynamic. The most relevant nuage structure with mitochondria is IMC, also called pi-body, present in prospermatogonia, spermatogonia, and spermatocytes. IMC is primarily enriched with various Piwi-interacting RNA (piRNA) proteins and mainly functions as piRNA biogenesis, transposon silencing, mRNA translation, and mitochondria fusion. Importantly, our previous work reported that mitochondria-associated ER membranes (MAMs) are abundant in spermatogenic cells and contain many crucial proteins associated with the piRNA pathway. Provocatively, IMC functionally communicates with other nuage structures, such as piP-body, to perform its complex functions in spermatogenesis. Although little is known about the formation of both IMC and MAMs, its distinctive characters have attracted considerable attention. Here, we review the insights gained from studying the structural components of mitochondria-associated germinal structures, including IMC, CB, and MAMs, which are pivotal structures to ensure genome integrity and male fertility. We discuss the roles of the structural components in spermatogenesis and piRNA biogenesis, which provide new insights into mitochondria-associated germinal structures in germ cell development and male reproduction.

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

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

scholarly journals piRNA-guided co-transcriptional silencing coopts nuclear export factors

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Martin H Fabry ◽  
Filippo Ciabrelli ◽  
Marzia Munafò ◽  
Evelyn L Eastwood ◽  
Emma Kneuss ◽  
...  
Keyword(s):  
Transcriptional Repression ◽  
Nuclear Export ◽  
Rna Binding ◽  
Transcriptional Silencing ◽  
Genome Integrity ◽  
Terminal Portion ◽  
Amino Terminal ◽  
Repressive Chromatin ◽  
Binding Event ◽  
Pirna Pathway

The PIWI-interacting RNA (piRNA) pathway is a small RNA-based immune system that controls the expression of transposons and maintains genome integrity in animal gonads. In Drosophila, piRNA-guided silencing is achieved, in part, via co-transcriptional repression of transposons by Piwi. This depends on Panoramix (Panx); however, precisely how an RNA binding event silences transcription remains to be determined. Here we show that Nuclear Export Factor 2 (Nxf2) and its co-factor, Nxt1, form a complex with Panx and are required for co-transcriptional silencing of transposons in somatic and germline cells of the ovary. Tethering of Nxf2 or Nxt1 to RNA results in silencing of target loci and the concomitant accumulation of repressive chromatin marks. Nxf2 and Panx proteins are mutually required for proper localization and stability. We mapped the protein domains crucial for the Nxf2/Panx complex formation and show that the amino-terminal portion of Panx is sufficient to induce transcriptional silencing.

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