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.

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 Golden hamster piRNAs are necessary for early embryonic development and establishment of spermatogonia

2021 ◽  
Author(s):  
Zuzana Loubalova ◽  
Helena Fulka ◽  
Filip Horvat ◽  
Josef Pasulka ◽  
Radek Malik ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Golden Hamster ◽  
Developmental Competence ◽  
Early Embryonic Development ◽  
Spermatogenic Cells ◽  
Adaptive Nature ◽  
Pirna Pathway

ABSTRACTPIWI-associated RNAs (piRNAs) support the germline by suppressing retrotransposons and genes. In mice, piRNAs are essential for spermatogenesis but not oogenesis. To test how this applies to other mammals, we deleted Mov10l1 helicase in golden hamster, whose piRNA pathway is configured more similarly to that of other mammals. Mov10l1−/− male hamsters showed impaired establishment of spermatogonia accompanied by transcriptome dysregulation and a surge in MYSERV retrotransposon expression. The rare viable spermatogenic cells showed a meiotic failure phenotype like Mov10l1−/− mice. Female Mov10l1−/− hamsters were sterile due to post-meiotic loss of developmental competence in zygotes. Unique phenotypes of Mov10l1−/− hamsters demonstrate the adaptive nature of piRNA-mediated control of genes and retrotransposons in order to confront emerging genomic threats or acquire new physiological roles.

scholarly journals Maybe repressed mRNAs are not stored in the chromatoid body in mammalian spermatids

Reproduction ◽  
2011 ◽  
Vol 142 (3) ◽  
pp. 383-388 ◽  
Author(s):  
Kenneth C Kleene ◽  
Danielle L Cullinane
Keyword(s):  
Caenorhabditis Elegans ◽  
Mrna Translation ◽  
Mrna Localization ◽  
Structure And Function ◽  
Convincing Evidence ◽  
Chromatoid Body ◽  
P Granules ◽  
Accurate Indication ◽  
And Function ◽  
Translational Apparatus

The chromatoid body is a dynamic organelle that is thought to coordinate the cytoplasmic regulation of mRNA translation and degradation in mammalian spermatids. The chromatoid body is also postulated to function in repression of mRNA translation by sequestering dormant mRNAs where they are inaccessible to the translational apparatus. This review finds no convincing evidence that dormant mRNAs are localized exclusively in the chromatoid body. This discrepancy can be explained by two hypotheses. First, experimental artifacts, possibly related to peculiarities of the structure and function of the chromatoid body, preclude obtaining an accurate indication of mRNA localization. Second, mRNA is not stored in the chromatoid body, because, like perinuclear P granules in Caenorhabditis elegans, the chromatoid body functions as a center for mRNP remodeling and export to other cytoplasmic sites.

scholarly journals Assembly and Function of Gonad-Specific Non-Membranous Organelles in Drosophila piRNA Biogenesis

2019 ◽  
Vol 5 (4) ◽  
pp. 52 ◽  
Author(s):  
Shigeki Hirakata ◽  
Mikiko C. Siomi
Keyword(s):  
Dna Damage ◽  
Gonadal Development ◽  
Mitochondrial Membranes ◽  
Animal Life ◽  
Transposon Silencing ◽  
Dna Elements ◽  
Non Coding Rnas ◽  
And Function ◽  
Pirna Pathway

PIWI-interacting RNAs (piRNAs) are small non-coding RNAs that repress transposons in animal germlines. This protects the genome from the invasive DNA elements. piRNA pathway failures lead to DNA damage, gonadal development defects, and infertility. Thus, the piRNA pathway is indispensable for the continuation of animal life. piRNA-mediated transposon silencing occurs in both the nucleus and cytoplasm while piRNA biogenesis is a solely cytoplasmic event. piRNA production requires a number of proteins, the majority of which localize to non-membranous organelles that specifically appear in the gonads. Other piRNA factors are localized on outer mitochondrial membranes. In situ RNA hybridization experiments show that piRNA precursors are compartmentalized into other non-membranous organelles. In this review, we summarize recent findings about the function of these organelles in the Drosophila piRNA pathway by focusing on their assembly and function.

scholarly journals poly(UG)-tailed RNAs in Genome Protection and Epigenetic Inheritance

2019 ◽  
Author(s):  
Aditi Shukla ◽  
Jenny Yan ◽  
Daniel J. Pagano ◽  
Anne E. Dodson ◽  
Yuhan Fei ◽  
...  
Keyword(s):  
Gene Silencing ◽  
Epigenetic Inheritance ◽  
Genome Integrity ◽  
Small Interfering Rnas ◽  
Genetic Elements ◽  
C Elegans ◽  
Transposon Silencing ◽  
Rna Fragments ◽  
Heterologous Expression Systems ◽  
Genome Protection

AbstractMobile genetic elements threaten genome integrity in all organisms. MUT-2/RDE-3 is a ribonucleotidyltransferase required for transposon silencing and RNA interference (RNAi) in C. elegans. When tethered to RNAs in heterologous expression systems, RDE-3 can add long stretches of alternating non-templated uridine (U) and guanosine (G) ribonucleotides to the 3’ termini of these RNAs (polyUG or pUG tails). Here, we show that, in its natural context in C. elegans, RDE-3 adds pUG tails to transposon RNAs, as well as to targets of RNAi. pUG tails with more than 16 perfectly alternating 3’ U and G nucleotides convert otherwise inert RNA fragments into agents of gene silencing. pUG tails promote gene silencing by recruiting RNA-dependent RNA Polymerases (RdRPs), which use pUG-tailed RNAs as templates to synthesize small interfering RNAs (siRNAs). Cycles of pUG RNA-templated siRNA synthesis and siRNA-directed mRNA pUGylation underlie dsRNA-directed transgenerational epigenetic inheritance in the C. elegans germline. Our results show that pUG tails convert RNAs into transgenerational memories of past gene silencing events, which, we speculate, allow parents to inoculate progeny against the expression of unwanted or parasitic genetic elements.

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 Specialization of the Drosophila nuclear export family protein, Nxf3, for piRNA precursor export

2019 ◽  
Author(s):  
Emma Kneuss ◽  
Marzia Munafò ◽  
Evelyn L. Eastwood ◽  
Undine-Sophie Deumer ◽  
Jonathan B. Preall ◽  
...  
Keyword(s):  
Rna Polymerase Ii ◽  
Small Rna ◽  
Nuclear Export ◽  
Mrna Export ◽  
Transposon Silencing ◽  
Family Protein ◽  
Pirna Pathway ◽  
Harmful Effects ◽  
Shed Light ◽  
Mature Mrnas

AbstractThe piRNA pathway is a conserved, small RNA-based immune system that protects animal germ cell genomes from the harmful effects of transposon mobilisation. In Drosophila ovaries, most piRNAs originate from dual-strand clusters, which generate piRNAs from both genomic strands. Dual-strand clusters use non-canonical transcription mechanisms. Although transcribed by RNA polymerase II, cluster transcripts lack splicing signatures and poly(A) tails. mRNA processing is important for general mRNA export mediated by Nuclear export factor 1. Although UAP56, a component of the transcription and export complex, has been implicated in piRNA precursor export, it remains unknown how dual-strand cluster transcripts are specifically targeted for piRNA biogenesis by export from the nucleus to cytoplasmic processing centers. Here we report that dual-strand cluster transcript export requires CG13741/Bootlegger and the Drosophila Nuclear export factor family protein, Nxf3. Bootlegger is specifically recruited to piRNA clusters and in turn brings Nxf3. We find that Nxf3 specifically binds to piRNA precursors and is essential for their export to piRNA biogenesis sites, a process that is critical for germline transposon silencing. Our data shed light on how dual-strand clusters compensate for a lack of canonical features of mature mRNAs to be specifically exported via Nxf3, ensuring proper piRNA production.

scholarly journals Somatic piRNAs and Transposons are Differentially Expressed Coincident with Skeletal Muscle Atrophy and Programmed Cell Death

2021 ◽  
Vol 12 ◽  
Author(s):  
Junko Tsuji ◽  
Travis Thomson ◽  
Christine Brown ◽  
Subhanita Ghosh ◽  
William E. Theurkauf ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Skeletal Muscle Atrophy ◽  
Rna Seq ◽  
Developmentally Regulated ◽  
Transposon Silencing ◽  
Ping Pong ◽  
Somatic Tissues ◽  
Oxidation Resistant ◽  
Pirna Pathway

PIWI-interacting RNAs (piRNAs) are small single-stranded RNAs that can repress transposon expression via epigenetic silencing and transcript degradation. They have been identified predominantly in the ovary and testis, where they serve essential roles in transposon silencing in order to protect the integrity of the genome in the germline. The potential expression of piRNAs in somatic cells has been controversial. In the present study we demonstrate the expression of piRNAs derived from both genic and transposon RNAs in the intersegmental muscles (ISMs) from the tobacco hawkmoth Manduca sexta. These piRNAs are abundantly expressed, ∼27 nt long, map antisense to transposons, are oxidation resistant, exhibit a 5’ uridine bias, and amplify via the canonical ping-pong pathway. An RNA-seq analysis demonstrated that 19 piRNA pathway genes are expressed in the ISMs and are developmentally regulated. The abundance of piRNAs does not change when the muscles initiate developmentally-regulated atrophy, but are repressed coincident with the commitment of the muscles undergo programmed cell death at the end of metamorphosis. This change in piRNA expression is correlated with the repression of several retrotransposons and the induction of specific DNA transposons. The developmentally-regulated changes in the expression of piRNAs, piRNA pathway genes, and transposons are all regulated by 20-hydroxyecdysone, the steroid hormone that controls the timing of ISM death. Taken together, these data provide compelling evidence for the existence of piRNA in somatic tissues and suggest that they may play roles in developmental processes such as programmed cell death.

scholarly journals Channel Nuclear Pore Complex subunits are required for transposon silencing in Drosophila

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Marzia Munafò ◽  
Victoria R Lawless ◽  
Alessandro Passera ◽  
Serena MacMillan ◽  
Susanne Bornelöv ◽  
...  
Keyword(s):  
Nuclear Pore Complex ◽  
Selective Pressure ◽  
Ovarian Follicle ◽  
Follicle Cells ◽  
Nuclear Pore ◽  
Tissue Specific ◽  
Transposon Silencing ◽  
Multiple Copies ◽  
Pirna Pathway ◽  
Inner Channel

The Nuclear Pore Complex (NPC) is the principal gateway between nucleus and cytoplasm that enables exchange of macromolecular cargo. Composed of multiple copies of ~30 different nucleoporins (Nups), the NPC acts as a selective portal, interacting with factors which individually license passage of specific cargo classes. Here we show that two Nups of the inner channel, Nup54 and Nup58, are essential for transposon silencing via the PIWI-interacting RNA (piRNA) pathway in the Drosophila ovary. In ovarian follicle cells, loss of Nup54 and Nup58 results in compromised piRNA biogenesis exclusively from the flamenco locus, whereas knockdowns of other NPC subunits have widespread consequences. This provides evidence that some nucleoporins can acquire specialised roles in tissue-specific contexts. Our findings consolidate the idea that the NPC has functions beyond simply constituting a barrier to nuclear/cytoplasmic exchange, as genomic loci subjected to strong selective pressure can exploit NPC subunits to facilitate their expression.

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