scholarly journals Starvation-Induced Transgenerational Inheritance of Small RNAs in C. elegans

Cell ◽  
2014 ◽  
Vol 158 (2) ◽  
pp. 277-287 ◽  
Author(s):  
Oded Rechavi ◽  
Leah Houri-Ze’evi ◽  
Sarit Anava ◽  
Wee Siong Sho Goh ◽  
Sze Yen Kerk ◽  
...  
Keyword(s):  
Small Rnas ◽  
Transgenerational Inheritance ◽  
C Elegans

scholarly journals Stress Resets Transgenerational Small RNA Inheritance

2019 ◽  
Author(s):  
Leah Houri-Ze’evi ◽  
Guy Teichman ◽  
Hila Gingold ◽  
Oded Rechavi
Keyword(s):  
Small Rna ◽  
Small Rnas ◽  
Memory Trace ◽  
Mapk Pathway ◽  
Transgenerational Inheritance ◽  
Cultivation Conditions ◽  
C Elegans ◽  
Genome Wide ◽  
A Genome ◽  
Basic Concepts

AbstractTransgenerational inheritance of small RNAs is challenging basic concepts of heredity and achieving control over such responses is of great interest. InC. elegansnematodes, small RNAs are transmitted across generations to establish a transgenerational memory trace of ancestral environments and distinguish self from non-self genes. Inheritance of small RNAs is regulated by dedicated machinery and carryover of aberrant heritable small RNA responses was shown to be maladaptive and to induce sterility. Here we show that various types of stress (starvation, high temperatures, and high osmolarity) but not non-stressful changes in cultivation conditions, lead to resetting of small RNA inheritance. We found that stress leads to a genome-wide reduction in heritable small RNA levels and that mutants defective in different stress pathways exhibit irregular RNAi inheritance dynamics. Moreover, we discovered that resetting of heritable RNAi is orchestrated by MAPK pathway factors, the transcription factor SKN-1, and the MET-2 methyltransferase. Termination of small RNA inheritance, and the fact that this process depends on stress, could protect from run-on of environment-irrelevant heritable gene regulation.

scholarly journals Cross-kingdom recognition of bacterial small RNAs induces transgenerational pathogenic avoidance

2019 ◽  
Author(s):  
Rachel Kaletsky ◽  
Rebecca S. Moore ◽  
Lance L. Parsons ◽  
Coleen T. Murphy
Keyword(s):  
Small Rnas ◽  
Pathogenic Bacteria ◽  
Escape Behavior ◽  
Bacterial Species ◽  
Future Generations ◽  
Transgenerational Inheritance ◽  
Signaling System ◽  
Specific Behavior ◽  
C Elegans ◽  
Species Specific

AbstractWe recently discovered that C. elegans can pass on a learned avoidance of pathogenic Pseudomonas aeruginosa (PA14) to four generations of its progeny. This transgenerational inheritance is bacterial species-specific, but how C. elegans recognizes and distinguishes different bacteria and transmits this information to future generations is not apparent. Here we show that small RNAs purified from pathogenic PA14 are sufficient not only to induce avoidance of pathogens in mothers, but also to confer transgenerational inheritance of this species-specific behavior for four generations, all without direct contact with pathogenic bacteria. This behavior requires the small RNA transporters SID-1 and SID-2, RNA interference pathway components, the piRNA Piwi/Argonaute pathway, a functioning germline, and TGF-β ligand daf-7 expression in the ASI sensory neuron. Our results suggest that C. elegans “reads” small RNAs expressed by pathogenic bacteria, and uses this information to induce an escape behavior that lasts for four additional generations. C. elegans may have evolved this trans-kingdom signaling system to avoid pathogens in abundant classes of bacteria in its environment and its microbiome.

scholarly journals Stress resets ancestral heritable small RNA responses

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Leah Houri Zeevi ◽  
Guy Teichman ◽  
Hila Gingold ◽  
Oded Rechavi
Keyword(s):  
Small Rna ◽  
Small Rnas ◽  
Memory Trace ◽  
Mapk Pathway ◽  
Transgenerational Inheritance ◽  
C Elegans ◽  
Genome Wide ◽  
A Genome ◽  
Basic Concepts ◽  
Stress Dependent

Transgenerational inheritance of small RNAs challenges basic concepts of heredity. In C. elegans nematodes, small RNAs are transmitted across generations to establish a transgenerational memory trace of ancestral environments and distinguish self-genes from non-self-elements. Carryover of aberrant heritable small RNA responses was shown to be maladaptive and to lead to sterility. Here we show that various types of stress (starvation, high temperatures, and high osmolarity) induce resetting of ancestral small RNA responses and a genome-wide reduction in heritable small RNA levels. We found that mutants that are defective in various stress pathways exhibit irregular RNAi inheritance dynamics even in the absence of stress. Moreover, we discovered that resetting of ancestral RNAi responses is specifically orchestrated by factors that function in the p38 MAPK pathway and the transcription factor SKN-1/Nrf2. Stress-dependent termination of small RNA inheritance could protect from run-on of environment-irrelevant heritable gene regulation.

scholarly journals The secreted endoribonuclease ENDU-2 from the soma protects germline immortality in C. elegans

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Wenjing Qi ◽  
Erika D. V. Gromoff ◽  
Fan Xu ◽  
Qian Zhao ◽  
Wei Yang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Small Rnas ◽  
C Elegans ◽  
Cleavage Activity ◽  
Response To Temperature ◽  
Multicellular Organisms ◽  
Cell Immortality ◽  
Mature Mrnas ◽  
Endoribonuclease Activity

AbstractMulticellular organisms coordinate tissue specific responses to environmental information via both cell-autonomous and non-autonomous mechanisms. In addition to secreted ligands, recent reports implicated release of small RNAs in regulating gene expression across tissue boundaries. Here, we show that the conserved poly-U specific endoribonuclease ENDU-2 in C. elegans is secreted from the soma and taken-up by the germline to ensure germline immortality at elevated temperature. ENDU-2 binds to mature mRNAs and negatively regulates mRNA abundance both in the soma and the germline. While ENDU-2 promotes RNA decay in the soma directly via its endoribonuclease activity, ENDU-2 prevents misexpression of soma-specific genes in the germline and preserves germline immortality independent of its RNA-cleavage activity. In summary, our results suggest that the secreted RNase ENDU-2 regulates gene expression across tissue boundaries in response to temperature alterations and contributes to maintenance of stem cell immortality, probably via retaining a stem cell specific program of gene expression.

scholarly journals E. coli OxyS non-coding RNA does not trigger RNAi in C. elegans

2014 ◽  
Author(s):  
Alper Akay ◽  
Peter Sarkies ◽  
Eric Alexander Miska
Keyword(s):  
Small Rnas ◽  
Biological Function ◽  
Rapid Development ◽  
Rnai Pathway ◽  
Regulate Gene Expression ◽  
Double Stranded Rna ◽  
E Coli ◽  
C Elegans ◽  
Non Coding Rna ◽  
Rnai Response

The discovery of RNA interference (RNAi) in C. elegans has had a major impact on scientific research, led to the rapid development of RNAi tools and has inspired RNA-based therapeutics. Astonishingly, nematodes, planaria and many insects take up double-stranded RNA (dsRNA) from their environment to elicit RNAi; the biological function of this mechanism is unclear. Recently, the E. coli OxyS non-coding RNA was shown to regulate gene expression in C. elegans when E. coli is offered as food. This was surprising given that C. elegans is unlikely to encounter E. coli in nature. To directly test the hypothesis that the E. coli OxyS non-coding RNA triggers the C. elegans RNAi pathway, we sequenced small RNAs from C. elegans after feeding with bacteria. We clearly demonstrate that the OxyS non-coding RNA does not trigger an RNAi response in C. elegans. We conclude that the biology of environmental RNAi remains to be discovered.

scholarly journals Long-term experimental evolution reveals purifying selection on piRNA-mediated control of transposable element expression

BMC Biology ◽  
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Ulfar Bergthorsson ◽  
Caroline J. Sheeba ◽  
Anke Konrad ◽  
Tony Belicard ◽  
Toni Beltran ◽  
...  
Keyword(s):  
Natural Selection ◽  
Transcriptional Activation ◽  
Small Rnas ◽  
Active Regions ◽  
Purifying Selection ◽  
Ancestral Population ◽  
Sequence Context ◽  
C Elegans ◽  
Population Sizes

Abstract Background Transposable elements (TEs) are an almost universal constituent of eukaryotic genomes. In animals, Piwi-interacting small RNAs (piRNAs) and repressive chromatin often play crucial roles in preventing TE transcription and thus restricting TE activity. Nevertheless, TE content varies widely across eukaryotes and the dynamics of TE activity and TE silencing across evolutionary time is poorly understood. Results Here, we used experimentally evolved populations of C. elegans to study the dynamics of TE expression over 409 generations. The experimental populations were evolved at population sizes of 1, 10 and 100 individuals to manipulate the efficiency of natural selection versus genetic drift. We demonstrate increased TE expression relative to the ancestral population, with the largest increases occurring in the smallest populations. We show that the transcriptional activation of TEs within active regions of the genome is associated with failure of piRNA-mediated silencing, whilst desilenced TEs in repressed chromatin domains retain small RNAs. Additionally, we find that the sequence context of the surrounding region influences the propensity of TEs to lose silencing through failure of small RNA-mediated silencing. Conclusions Our results show that natural selection in C. elegans is responsible for maintaining low levels of TE expression, and provide new insights into the epigenomic features responsible.

scholarly journals Caenorhabditis elegans Deficient in DOT-1.1 Exhibit Increases in H3K9me2 at Enhancer and Certain RNAi-Regulated Regions

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1846 ◽  
Author(s):  
Ruben Esse ◽  
Alla Grishok
Keyword(s):  
Small Rnas ◽  
Mammalian Cells ◽  
Leukemic Cells ◽  
Rnai Pathway ◽  
Open Chromatin ◽  
Loss Of Function ◽  
Promoter Regions ◽  
Heterochromatin Formation ◽  
C Elegans ◽  
H3k79 Methylation

The methylation of histone H3 at lysine 79 is a feature of open chromatin. It is deposited by the conserved histone methyltransferase DOT1. Recently, DOT1 localization and H3K79 methylation (H3K79me) have been correlated with enhancers in C. elegans and mammalian cells. Since earlier research implicated H3K79me in preventing heterochromatin formation both in yeast and leukemic cells, we sought to inquire whether a H3K79me deficiency would lead to higher levels of heterochromatic histone modifications, specifically H3K9me2, at developmental enhancers in C. elegans. Therefore, we used H3K9me2 ChIP-seq to compare its abundance in control and dot-1.1 loss-of-function mutant worms, as well as in rde-4; dot-1.1 and rde-1; dot-1.1 double mutants. The rde-1 and rde-4 genes are components of the RNAi pathway in C. elegans, and RNAi is known to initiate H3K9 methylation in many organisms, including C. elegans. We have previously shown that dot-1.1(−) lethality is rescued by rde-1 and rde-4 loss-of-function. Here we found that H3K9me2 was elevated in enhancer, but not promoter, regions bound by the DOT-1.1/ZFP-1 complex in dot-1.1(−) worms. We also found increased H3K9me2 at genes targeted by the ALG-3/4-dependent small RNAs and repeat regions. Our results suggest that ectopic H3K9me2 in dot-1.1(−) could, in some cases, be induced by small RNAs.

scholarly journals Small RNAs in parasitic nematodes – forms and functions

Parasitology ◽  
2019 ◽  
Vol 147 (8) ◽  
pp. 855-864
Author(s):  
Collette Britton ◽  
Roz Laing ◽  
Eileen Devaney
Keyword(s):  
Gene Expression ◽  
Small Rna ◽  
Small Rnas ◽  
Target Genes ◽  
Parasitic Nematodes ◽  
Small Rna Sequencing ◽  
Small Interfering Rnas ◽  
Rna Sequences ◽  
C Elegans

AbstractSmall RNAs are important regulators of gene expression. They were first identified in Caenorhabditis elegans, but it is now apparent that the main small RNA silencing pathways are functionally conserved across diverse organisms. Availability of genome data for an increasing number of parasitic nematodes has enabled bioinformatic identification of small RNA sequences. Expression of these in different lifecycle stages is revealed by small RNA sequencing and microarray analysis. In this review we describe what is known of the three main small RNA classes in parasitic nematodes – microRNAs (miRNAs), Piwi-interacting RNAs (piRNAs) and small interfering RNAs (siRNAs) – and their proposed functions. miRNAs regulate development in C. elegans and the temporal expression of parasitic nematode miRNAs suggest modulation of target gene levels as parasites develop within the host. miRNAs are also present in extracellular vesicles released by nematodes in vitro, and in plasma from infected hosts, suggesting potential regulation of host gene expression. Roles of piRNAs and siRNAs in suppressing target genes, including transposable elements, are also reviewed. Recent successes in RNAi-mediated gene silencing, and application of small RNA inhibitors and mimics will continue to advance understanding of small RNA functions within the parasite and at the host–parasite interface.

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