PIWI-interacting RNAs (piRNAs) support the germline by suppressing retrotransposons. Studies of the pathway in mice have strongly shaped the view that mammalian piRNAs are essential for male but not for female fertility. Here, we report that the role of the piRNA pathway substantially differs in golden hamsters (Mesocricetus auratus), the piRNA pathway setup of which more closely resembles that of other mammals, including humans. The loss of the Mov10l1 RNA helicase-an essential piRNA biogenesis factor-leads to striking phenotypes in both sexes. In contrast to mice, female Mov10l1-/- hamsters are sterile because their oocytes do not sustain zygotic development. Furthermore, Mov10l1-/- male hamsters have impaired establishment of spermatogonia accompanied by transcriptome dysregulation and an expression surge of a young retrotransposon subfamily. Our results show that the mammalian piRNA pathway has essential roles in both sexes and its adaptive nature allows it to manage emerging genomic threats and acquire new critical roles in the germline.

• MeSH
• křečci praví MeSH
• křeček rodu Mesocricetus metabolismus   MeSH
• malá interferující RNA genetika   MeSH
• oocyty metabolismus   patologie   MeSH
• retroelementy fyziologie   MeSH
• RNA-helikasy genetika   MeSH
• spermatogeneze genetika   fyziologie   MeSH
• spermatogonie metabolismus   patologie   MeSH
• testis metabolismus   MeSH
• umlčování genů fyziologie   MeSH
• zvířata MeSH
• Check Tag
• křečci praví MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

PIWI-interacting RNAs (piRNAs) play a crucial role in safeguarding genome integrity by silencing mobile genetic elements. From flies to humans, piRNAs originate from long single-stranded precursors encoded by genomic piRNA clusters. How piRNA clusters form to adapt to genomic invaders and evolve to maintain protection remain key outstanding questions. Here, we generate a roadmap of piRNA clusters across seven species that highlights both similarities and variations. In mammals, we identify transcriptional readthrough as a mechanism to generate piRNAs from transposon insertions (piCs) downstream of genes (DoG). Together with the well-known stress-dependent DoG transcripts, our findings suggest a molecular mechanism for the formation of piRNA clusters in response to retroviral invasion. Finally, we identify a class of dynamic piRNA clusters in humans, underscoring unique features of human germ cell biology. Our results advance the understanding of conserved principles and species-specific variations in piRNA biology and provide tools for future studies.

• MeSH
• druhová specificita MeSH
• lidé MeSH
• malá interferující RNA * metabolismus   genetika   MeSH
• myši MeSH
• Piwi-interagující RNA MeSH
• psi MeSH
• savci * genetika   MeSH
• transpozibilní elementy DNA genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• psi MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

PIWI-interacting RNAs (piRNAs) and their associated PIWI clade Argonaute proteins constitute the core of the piRNA pathway. In gonadal cells, this conserved pathway is crucial for genome defense, and its main function is to silence transposable elements. This is achieved through posttranscriptional and transcriptional gene silencing. Precursors that give rise to piRNAs require specialized transcription and transport machineries because piRNA biogenesis is a cytoplasmic process. The ping-pong cycle, a posttranscriptional silencing mechanism, combines the cleavage-dependent silencing of transposon RNAs with piRNA production. PIWI proteins also function in the nucleus, where they scan for nascent target transcripts with sequence complementarity, instructing transcriptional silencing and deposition of repressive chromatin marks at transposon loci. Although studies have revealed numerous factors that participate in each branch of the piRNA pathway, the precise molecular roles of these factors often remain unclear. In this review, we summarize our current understanding of the mechanisms involved in piRNA biogenesis and function.

• MeSH
• Argonaut proteiny genetika   MeSH
• Drosophila melanogaster genetika   MeSH
• genetická transkripce * MeSH
• gonády růst a vývoj   MeSH
• malá interferující RNA biosyntéza   genetika   MeSH
• transpozibilní elementy DNA genetika   MeSH
• umlčování genů MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Small noncoding RNAs play an important role in various disease states, including cancer. PIWI proteins, a subfamily of Argonaute proteins, and PIWI-interacting RNAs (piRNAs) were originally described as germline-specific molecules that inhibit the deleterious activity of transposable elements. However, several studies have suggested a role for the piRNA-PIWI axis in somatic cells, including somatic stem cells. Dysregulated expression of piRNAs and PIWI proteins in human tumors implies that, analogously to their roles in undifferentiated cells under physiological conditions, these molecules may be important for cancer stem cells and thus contribute to cancer progression. We provide an overview of piRNA biogenesis and critically review the evidence for the role of piRNA-PIWI axis in cancer stem cells. In addition, we examine the potential of piRNAs and PIWI proteins to become biomarkers in cancer.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The PIWI-interacting RNA (piRNA) pathway is a conserved defense mechanism that protects the genetic information of animal germ cells from the deleterious effects of molecular parasites, such as transposons. Discovered nearly a decade ago, this small RNA silencing system comprises PIWI-clade Argonaute proteins and their associated RNA-binding partners, the piRNAs. In this review, we highlight recent work that has advanced our understanding of how piRNAs preserve genome integrity across generations. We discuss the mechanism of piRNA biogenesis, give an overview of common themes as well as differences in piRNA-mediated silencing between species, and end by highlighting known and emerging functions of piRNAs.

• MeSH
• Argonaut proteiny genetika   metabolismus   MeSH
• chromozomální proteiny, nehistonové genetika   metabolismus   MeSH
• Drosophila melanogaster genetika   metabolismus   MeSH
• genetická transkripce MeSH
• histony genetika   metabolismus   MeSH
• lidé MeSH
• malá interferující RNA genetika   metabolismus   MeSH
• messenger RNA genetika   metabolismus   MeSH
• proteiny asociované s mikrotubuly genetika   metabolismus   MeSH
• proteiny Drosophily genetika   metabolismus   MeSH
• proteiny vázající RNA genetika   metabolismus   MeSH
• umlčování genů * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Osteoarthritis (OA) is a frequent musculoskeletal disorder affecting millions of people worldwide. Despite advances in understanding the pathogenesis of OA, prognostic biomarkers or effective targeted treatment are not currently available. Research on epigenetic factors has yielded some new insights as new technologies for their detection continue to emerge. In this context, non-coding RNAs, including microRNAs, long non-coding RNAs, circular RNAs, piwi-interacting RNAs, and small nucleolar RNAs, regulate intracellular signaling pathways and biological processes that have a crucial role in the development of several diseases. In this review, we present current knowledge on the role of epigenetic factors with a focus on non-coding RNAs in the development, prediction and treatment of OA. This article is categorized under: RNA in Disease and Development > RNA in Disease.

• MeSH
• kruhová RNA MeSH
• lidé MeSH
• mikro RNA * genetika   MeSH
• osteoartróza * genetika   MeSH
• Piwi-interagující RNA MeSH
• RNA dlouhá nekódující * genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Germline genome defense evolves to recognize and suppress retrotransposons. One of defensive mechanisms is the PIWI-associated RNA (piRNA) pathway, which employs small RNAs for sequence-specific repression. The loss of the piRNA pathway in mice causes male sterility while females remain fertile. Unlike spermatogenic cells, mouse oocytes posses also RNA interference (RNAi), another small RNA pathway capable of retrotransposon suppression. To examine whether RNAi compensates the loss of the piRNA pathway, we produced a new RNAi pathway mutant DicerSOM and crossed it with a catalytically-dead mutant of Mili, an essential piRNA gene. Normal follicular and oocyte development in double mutants showed that RNAi does not suppress a strong ovarian piRNA knock-out phenotype. However, we observed redundant and non-redundant targeting of specific retrotransposon families illustrating stochasticity of recognition and targeting of invading retrotransposons. Intracisternal A Particle retrotransposon was mainly targeted by the piRNA pathway, MaLR and RLTR10 retrotransposons were targeted mainly by RNAi. Double mutants showed accumulations of LINE-1 retrotransposon transcripts. However, we did not find strong evidence for transcriptional activation and mobilization of retrotransposition competent LINE-1 elements suggesting that while both defense pathways are simultaneously expendable for ovarian oocyte development, yet another transcriptional silencing mechanism prevents mobilization of LINE-1 elements.

• MeSH
• Argonaut proteiny genetika   MeSH
• DEAD-box RNA-helikasy genetika   MeSH
• malá interferující RNA genetika   MeSH
• mutace MeSH
• myši MeSH
• oocyty chemie   růst a vývoj   MeSH
• retroelementy * MeSH
• ribonukleasa III genetika   MeSH
• RNA interference * MeSH
• signální transdukce MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Transposable elements (TEs) are powerful drivers of genome evolutionary dynamics but are principally deleterious to the host organism by compromising the integrity and function of the genome. The transposition of TEs may result in mutations and DNA damage. DNA double-strand breaks (DSBs), which may be caused by the transposition, are one of the processes directly linked to aging. TEs may thus be considered to constitute an internal source of aging and the frequency of transposition may, in turn, be considered to affect the pace of aging. The PIWI-piRNA pathway is a widespread strategy used by most animals to effectively suppress transposition. Interestingly, the PIWI-piRNA pathway is expressed predominantly in the animal germline, a more or less continuous immortal lineage set aside after the first few cell divisions of a developing embryo. Recent findings further imply that the PIWI-piRNA pathway and TE suppression constitute an important mechanism regulating aging. This article discusses the proposed role of the PIWI-piRNA pathway in setting the pace of aging as well as the possible mechanisms underlying this process.

• MeSH
• Argonaut proteiny * genetika   metabolismus   MeSH
• buněčné dělení genetika   MeSH
• lidé MeSH
• malá interferující RNA * genetika   metabolismus   MeSH
• poškození DNA * MeSH
• stárnutí * genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

The Drosophila piRNA pathway provides an RNA-based immune system that defends the germline genome against selfish genetic elements. Two interrelated branches of the piRNA system exist: somatic cells that support oogenesis only employ Piwi, whereas germ cells utilize a more elaborate pathway centered on the three gonad-specific Argonaute proteins (Piwi, Aubergine, and Argonaute 3). While several key factors of each branch have been identified, our current knowledge is insufficient to explain the complex workings of the piRNA machinery. Here, we report a reverse genetic screen spanning the ovarian transcriptome in an attempt to uncover the full repertoire of genes required for piRNA-mediated transposon silencing in the female germline. Our screen reveals key factors of piRNA-mediated transposon silencing, including the piRNA biogenesis factors CG2183 (GASZ) and Deadlock. Our data uncover a previously unanticipated set of factors preferentially required for repression of different transposon types.

• MeSH
• Argonaut proteiny genetika   metabolismus   MeSH
• Drosophila melanogaster genetika   MeSH
• iniciační faktory genetika   metabolismus   MeSH
• malá interferující RNA genetika   metabolismus   MeSH
• ovarium fyziologie   MeSH
• proteiny asociované s mikrotubuly genetika   metabolismus   MeSH
• proteiny Drosophily genetika   metabolismus   MeSH
• reprodukovatelnost výsledků MeSH
• RNA interference * MeSH
• stanovení celkové genové exprese metody   MeSH
• transpozibilní elementy DNA * MeSH
• umlčování genů MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

Background: The early detection of colon cancer is one of the main prerequisites for successful treatment and mortality reduction. Circulating PIWI-interacting RNAs (piRNA) were recently identified as novel promising biomarkers. The purpose of the study was to assess the profiles of piRNAs in blood serum of colon cancer patients with the aim to identify those with high diagnostic potential.Methods: Blood serum samples from 403 colon cancer patients and 276 healthy donors were included in this 3-phase biomarker study. Large-scale piRNA expression profiling was performed using Illumina small RNA sequencing. The diagnostic potential of selected piRNAs was further validated on independent training and validation sets of samples using RT-qPCR.Results: In total, 31 piRNAs were found to be significantly deregulated in serum of cancer patients compared with healthy donors. Based on the levels of piR-5937 and piR-28876, it was possible to differentiate between cancer patients and healthy donors with high sensitivity and specificity. Moreover, both piRNAs exhibited satisfactory diagnostic performance also in patients with stage I disease and enabled detection of colon cancer with higher sensitivity than currently used biomarkers CEA and CA19-9. Finally, the expression of analyzed piRNAs in blood restored significantly 1 month after the surgical resection.Conclusions: Based on our findings, piRNAs are abundant in human blood serum. Furthermore, their levels in colon cancer have been observed to be significantly deregulated. However, their involvement in carcinogenesis must be further established.Impact: piRNAs could serve as promising noninvasive biomarkers for early detection of colon cancer. Cancer Epidemiol Biomarkers Prev; 27(9); 1019-28. ©2018 AACR.

• MeSH
• lidé středního věku MeSH
• lidé MeSH
• malá interferující RNA genetika   MeSH
• nádorové biomarkery genetika   MeSH
• nádory tračníku diagnóza   genetika   MeSH
• následné studie MeSH
• prognóza MeSH
• regulace genové exprese u nádorů * MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH