scholarly journals Environmentally-induced epigenetic conversion of a piRNA cluster

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Karine Casier ◽  
Valérie Delmarre ◽  
Nathalie Gueguen ◽  
Catherine Hermant ◽  
Elise Viodé ◽  
...  
Keyword(s):  
Environmental Changes ◽  
Maternal Inheritance ◽  
De Novo ◽  
P Element ◽  
Editorial Note ◽  
Double Stranded Rna ◽  
First Case ◽  
Pirna Cluster ◽  
Epigenetic Conversion

Transposable element (TE) activity is repressed in animal gonads by PIWI-interacting RNAs (piRNAs) produced by piRNA clusters. Current models in flies propose that germinal piRNA clusters are functionally defined by the maternal inheritance of piRNAs produced during the previous generation. Taking advantage of an inactive, but ready to go, cluster of P-element derived transgene insertions in Drosophila melanogaster, we show here that raising flies at high temperature (29°C) instead of 25°C triggers the stable conversion of this locus from inactive into actively producing functional piRNAs. The increase of antisense transcripts from the cluster at 29°C combined with the requirement of transcription of euchromatic homologous sequences, suggests a role of double stranded RNA in the production of de novo piRNAs. This report describes the first case of the establishment of an active piRNA cluster by environmental changes in the absence of maternal inheritance of homologous piRNAs.Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (<xref ref-type="decision-letter" rid="SA1">see decision letter</xref>).

scholarly journals Environmentally-induced epigenetic conversion of a piRNA cluster

2018 ◽  
Author(s):  
Karine Casier ◽  
Valérie Delmarre ◽  
Nathalie Gueguen ◽  
Catherine Hermant ◽  
Elise Viodé ◽  
...  
Keyword(s):  
High Temperature ◽  
Small Rnas ◽  
Environmental Changes ◽  
Maternal Inheritance ◽  
Natural Habitat ◽  
Minimal System ◽  
First Case ◽  
Pirna Cluster ◽  
Great Progress ◽  
Epigenetic Conversion

ABSTRACTTransposable element (TE) activity is repressed in animal gonads by PIWI-interacting RNAs (piRNAs), a class of small RNAs produced by specific loci made of TEs insertions and fragments. Current models propose that these loci are functionally defined by the maternal inheritance of piRNAs produced during the previous generation, raising the question of their first activation in the absence of piRNAs. Taking advantage of an inactive cluster of P-element derived transgene insertions, we show here that raising flies at high temperature (29°C) instead of 25°C results in a rare but invasive epigenetic conversion of this locus into an active piRNAs producing one. The newly acquired epigenetic state is stable over many generations even when flies are switch back to 25°C. The silencing capacities, piRNA production and chromatin modifications of the cluster are all identical whether conversion occurred by maternal piRNA inheritance or by high temperature. We also demonstrate that in addition to high temperature, a single homologous transgene inserted elsewhere in the genome is required to activate the locus. We thus have identified a minimal system of three components to create a stable piRNA producing locus: 1) a locus with multiple TE derived sequences; 2) an euchromatic copy of these sequences and 3) elevated temperature. Altogether, these data report the first case of the establishment of an active piRNA cluster by environmental changes. It highlights how such variations of species natural habitat can become heritable and shape their epigenome.SIGNIFICANCE STATEMENTRecently, we have witnessed great progress in our understanding of the silencing of Transposable Elements (TEs) by piRNAs, a class of small RNAs produced by piRNA clusters. At each generation, piRNA clusters are supposed to be activated by homologous piRNAs inherited from the mother raising the question of the making of the first piRNAs. Here, we report the birth of a stable and functional piRNA cluster induced by high temperature without maternal inheritance of homologous piRNAs. We propose a minimal system to create a piRNA cluster: a sufficient number of repeated sequences, a euchromatic copy of these sequences and an increase in the production of antisense RNA.

scholarly journals MORC3, a novel MIWI2 association partner, is an epigenetic regulator of piRNA-dependent transposon silencing.

2020 ◽  
Author(s):  
Toru Nakano ◽  
Satomi Kuramochi-Miyagawa ◽  
Manabu Nakayama ◽  
Haruhiko Koseki ◽  
Steven Jacobsen ◽  
...  
Keyword(s):  
Dna Methylation ◽  
De Novo ◽  
Effector Proteins ◽  
P Element ◽  
Effector Protein ◽  
Transposon Silencing ◽  
Epigenetic Regulator ◽  
Association Partner ◽  
Pirna Pathway

Abstract The PIWI (P-element-induced wimpy testis)-interacting-RNA (piRNA) pathway plays a crucial role in the repression of TE (transposable element) expression via de novo DNA methylation in mouse embryonic male germ cells. Various proteins, including MIWI2 are involved in the process. TE silencing is ensured by piRNA-guided MIWI2 that recruits some effector proteins of the DNA methylation machinery to TE regions. However, the molecular mechanism underlying the methylation is complex and has not been fully elucidated. Here, we identified MORC3 as a novel associating partner of MIWI2 and also a nuclear effector of retrotransposon silencing via piRNA-dependent de novo DNA methylation in embryonic testis. Moreover, we show that MORC3 is important for transcription of piRNA precursors and subsequently affects piRNA production. Thus, we provide the first mechanistic insights into the role of this effector protein in the first stage of piRNA biogenesis in embryonic TE silencing mechanism.

scholarly journals MORC3, a novel MIWI2 association partner, as an epigenetic regulator of piRNA dependent transposon silencing in male germ cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kanako Kojima-Kita ◽  
Satomi Kuramochi-Miyagawa ◽  
Manabu Nakayama ◽  
Haruhiko Miyata ◽  
Steven E. Jacobsen ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Germ Cells ◽  
De Novo ◽  
Effector Proteins ◽  
P Element ◽  
Male Germ Cells ◽  
Transposon Silencing ◽  
Association Partner ◽  
Pirna Pathway

AbstractThe PIWI (P-element-induced wimpy testis)-interacting-RNA (piRNA) pathway plays a crucial role in the repression of TE (transposable element) expression via de novo DNA methylation in mouse embryonic male germ cells. Various proteins, including MIWI2 are involved in the process. TE silencing is ensured by piRNA-guided MIWI2 that recruits some effector proteins of the DNA methylation machinery to TE regions. However, the molecular mechanism underlying the methylation is complex and has not been fully elucidated. Here, we identified MORC3 as a novel associating partner of MIWI2 and also a nuclear effector of retrotransposon silencing via piRNA-dependent de novo DNA methylation in embryonic testis. Moreover, we show that MORC3 is important for transcription of piRNA precursors and subsequently affects piRNA production. Thus, we provide the first mechanistic insights into the role of this effector protein in the first stage of piRNA biogenesis in embryonic TE silencing mechanism.

scholarly journals Back-priming mode of ϕ6 RNA-dependent RNA polymerase

2005 ◽  
Vol 86 (2) ◽  
pp. 521-526 ◽  
Author(s):  
Minni R. L. Laurila ◽  
Paula S. Salgado ◽  
David I. Stuart ◽  
Jonathan M. Grimes ◽  
Dennis H. Bamford
Keyword(s):  
Rna Polymerase ◽  
De Novo ◽  
Hepatitis C Virus Rna ◽  
Rna Dependent Rna Polymerase ◽  
Initiation Mechanism ◽  
Double Stranded Rna ◽  
Virus Rna ◽  
Structural Methods ◽  
Similar Element

The RNA-dependent RNA polymerase of the double-stranded RNA bacteriophage ϕ6 is capable of primer-independent initiation, as are many RNA polymerases. The structure of this polymerase revealed an initiation platform, composed of a loop in the C-terminal domain (QYKW, aa 629–632), that was essential for de novo initiation. A similar element has been identified in hepatitis C virus RNA-dependent RNA polymerase. Biochemical studies have addressed the role of this platform, revealing that a mutant version can utilize a back-priming initiation mechanism, where the 3′ terminus of the template adopts a hairpin-like conformation. Here, the mechanism of back-primed initiation is studied further by biochemical and structural methods.

Posttransplant CMV infection and the role of immunosuppression (Sponsor: Novartis Pharma GmbH, Nürnberg)

2016 ◽  
Vol 04 (01) ◽  
pp. 4-10
Keyword(s):  
Lower Incidence ◽  
Paradigm Shift ◽  
Mtor Inhibitor ◽  
De Novo ◽  
Expert Panel ◽  
Risk Of Infection ◽  
Cmv Infection ◽  
Expert Meeting ◽  
Selection Of

AbstractImmunosuppression permits graft survival after transplantation and consequently a longer and better life. On the other hand, it increases the risk of infection, for instance with cytomegalovirus (CMV). However, the various available immunosuppressive therapies differ in this regard. One of the first clinical trials using de novo everolimus after kidney transplantation [1] already revealed a considerably lower incidence of CMV infection in the everolimus arms than in the mycophenolate mofetil (MMF) arm. This result was repeatedly confirmed in later studies [2–4]. Everolimus is now considered a substance with antiviral properties. This article is based on the expert meeting “Posttransplant CMV infection and the role of immunosuppression”. The expert panel called for a paradigm shift: In a CMV prevention strategy the targeted selection of the immunosuppressive therapy is also a key element. For patients with elevated risk of CMV, mTOR inhibitor-based immunosuppression is advantageous as it is associated with a significantly lower incidence of CMV events.

249 ROLE OF DE NOVO LIPOGENESIS IN GROWING VERY LOW BIRTH WEIGHT BREASTFED INFANTS.

2004 ◽  
Vol 52 (Suppl 1) ◽  
pp. S122.6-S123
Author(s):  
M. Garg ◽  
C. Bell ◽  
L. Rogers ◽  
S. Bassilian ◽  
W. N.P. Lee
Keyword(s):  
Birth Weight ◽  
Low Birth Weight ◽  
Very Low Birth Weight ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
Breastfed Infants

scholarly journals Depression among health care students in the time of COVID-19: the mediating role of resilience in the hopelessness–depression relationship

2021 ◽  
pp. 008124632199445
Author(s):  
Tammy-lee Pretorius
Keyword(s):  
Health Care ◽  
Traumatic Event ◽  
National Level ◽  
Depression Scale ◽  
Health Care Students ◽  
Mediating Role ◽  
First Case ◽  
Hopelessness Depression ◽  
The World

COVID-19 spread rapidly across the world, and by March 2020, the first case of COVID-19 was identified in South Africa. Lockdown-related measures such as restricted movement and isolation were implemented to contain the virus. Combined with these measures, factors such as economic decline, job losses, and food shortages can cause numerous mental health sequelae such as depression. Feelings of hopelessness and helplessness as well as cases of suicide have been reported around the world due to the pandemic and the associated feelings of anxiety and depression. The aims of this study were to investigate levels of hopelessness and depression in a sample of health care students. A random sample of students ( N = 174) enrolled in a health sciences programme at the University of the Western Cape completed the Beck Hopelessness Scale, the Center for Epidemiological Studies Depression Scale, and a three-item Resilience Scale. The results revealed high levels of hopelessness and depression compared to previously reported normative data for these scales. In addition, the indirect effects of hopelessness on depression were significant, demonstrating the mediating role of resilience in the hopelessness–depression relationship. These results highlight a call for universities to take proactive measures in providing students with free and easily accessible resources to help them cope and manage stress during a traumatic event. More importantly, at a national level, preventive measures should be implemented to strengthen resilience in young adults.

scholarly journals Induction of Promoter DNA Methylation Upon High-Pressure Spraying of Double-Stranded RNA in Plants

Agronomy ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 789
Author(s):  
Athanasios Dalakouras ◽  
Ioannis Ganopoulos
Keyword(s):  
High Pressure ◽  
De Novo ◽  
Epigenetic Changes ◽  
Double Stranded Rna ◽  
Rna Molecules ◽  
Promoter Sequences ◽  
Promoter Dna Methylation ◽  
Promoter Dna ◽  
First Time ◽  
De Novo Methylation

Exogenous application of RNA molecules is a potent method to trigger RNA interference (RNAi) in plants in a transgene-free manner. So far, all exogenous RNAi (exo-RNAi) applications have aimed to trigger mRNA degradation of a given target. However, the issue of concomitant epigenetic changes was never addressed. Here, we report for the first time that high-pressure spraying of dsRNAs can trigger de novo methylation of promoter sequences in plants.

scholarly journals LncRNA CRNDE attenuates chemoresistance in gastric cancer via SRSF6-regulated alternative splicing of PICALM

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Feifei Zhang ◽  
Hui Wang ◽  
Jiang Yu ◽  
Xueqing Yao ◽  
Shibin Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Alternative Splicing ◽  
Noncoding Rna ◽  
De Novo ◽  
Acquired Resistance ◽  
Genetic Alterations ◽  
Clinical Samples ◽  
Autophagy Flux ◽  
Resistance To Chemotherapy

AbstractDe novo and acquired resistance, which are mainly mediated by genetic alterations, are barriers to effective routine chemotherapy. However, the mechanisms underlying gastric cancer (GC) resistance to chemotherapy are still unclear. We showed that the long noncoding RNA CRNDE was related to the chemosensitivity of GC in clinical samples and a PDX model. CRNDE was decreased and inhibited autophagy flux in chemoresistant GC cells. CRNDE directly bound to splicing protein SRSF6 to reduce its protein stability and thus regulate alternative splicing (AS) events. We determined that SRSF6 regulated the PICALM exon 14 skip splice variant and triggered a significant S-to-L isoform switch, which contributed to the expression of the long isoform of PICALM (encoding PICALML). Collectively, our findings reveal the key role of CRNDE in autophagy regulation, highlighting the significance of CRNDE as a potential prognostic marker and therapeutic target against chemoresistance in GC.

scholarly journals Genetic Studies of mei-P26 Reveal a Link Between the Processes That Control Germ Cell Proliferation in Both Sexes and Those That Control Meiotic Exchange in Drosophila

Genetics ◽  
2000 ◽  
Vol 155 (4) ◽  
pp. 1757-1772 ◽  
Author(s):  
Scott L Page ◽  
Kim S McKim ◽  
Benjamin Deneen ◽  
Tajia L Van Hook ◽  
R Scott Hawley
Keyword(s):  
Meiotic Recombination ◽  
Double Mutant ◽  
P Element ◽  
Genetic Studies ◽  
Germline Differentiation ◽  
Males And Females ◽  
Bag Of Marbles ◽  
Differentiation And Proliferation

Abstract We present the cloning and characterization of mei-P26, a novel P-element-induced exchange-defective female meiotic mutant in Drosophila melanogaster. Meiotic exchange in females homozygous for mei-P261 is reduced in a polar fashion, such that distal chromosomal regions are the most severely affected. Additional alleles generated by duplication of the P element reveal that mei-P26 is also necessary for germline differentiation in both females and males. To further assess the role of mei-P26 in germline differentiation, we tested double mutant combinations of mei-P26 and bag-of-marbles (bam), a gene necessary for the control of germline differentiation and proliferation in both sexes. A null mutation at the bam locus was found to act as a dominant enhancer of mei-P26 in both males and females. Interestingly, meiotic exchange in mei-P261; bamΔ86/+ females is also severely decreased in comparison to mei-P261 homozygotes, indicating that bam affects the meiotic phenotype as well. These data suggest that the pathways controlling germline differentiation and meiotic exchange are related and that factors involved in the mitotic divisions of the germline may regulate meiotic recombination.

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