scholarly journals A cytoplasmic Argonaute protein promotes the inheritance of RNAi

2017 ◽  
Author(s):  
Fei Xu ◽  
Xuezhu Feng ◽  
Xiangyang Chen ◽  
Chenchun Weng ◽  
Qi Yan ◽  
...  
Keyword(s):  
Early Embryogenesis ◽  
Rnai Pathway ◽  
Specific Information ◽  
Argonaute Protein ◽  
Rnai Machinery ◽  
Multiple Generations ◽  
C Elegans ◽  
Mrna Targets ◽  
Germline Genes ◽  
Nuclear Rnai

SummaryRNAi-elicited gene silencing is heritable and can persist for multiple generations after its initial induction in C. elegans. However, the mechanism by which parental-acquired trait-specific information from RNAi is inherited by the progenies is not fully understood. Here, we identified a cytoplasmic Argonaute protein, WAGO-4, necessary for the inheritance of RNAi. WAGO-4 exhibits asymmetrical translocation to the germline during early embryogenesis, accumulates at the perinuclear foci in the germline, and is required for the inheritance of exogenous RNAi targeting both germline- and soma-expressed genes. WAGO-4 binds to 22G-RNAs and their mRNA targets. Interestingly, WAGO-4-associated endogenous 22G-RNAs target the same cohort of germline genes as CSR-1 and contain untemplated addition of uracil at the 3’ ends. The poly(U) polymerase CDE-1 is required for the untemplated uridylation of 22G-RNAs and inheritance of RNAi. Therefore, we conclude that, in addition to the nuclear RNAi pathway, the cytoplasmic RNAi machinery also promotes RNAi inheritance.

scholarly journals Chromatin Compaction by Small RNAs and the Nuclear RNAi Machinery in C. elegans

2018 ◽  
Author(s):  
Brandon D. Fields ◽  
Scott Kennedy
Keyword(s):  
Small Rnas ◽  
Rna Binding ◽  
Higher Order ◽  
Post Translational Modification ◽  
Rnai Machinery ◽  
Regulate Gene Expression ◽  
Chromatin Compaction ◽  
C Elegans ◽  
Regulation Mechanisms ◽  
Nuclear Rnai

AbstractDNA is organized and compacted into higher-order structures in order to fit within nuclei and to facilitate proper gene regulation. Mechanisms by which higher order chromatin structures are established and maintained are poorly understood. In C. elegans, nuclear-localized small RNAs engage the nuclear RNAi machinery to regulate gene expression and direct the post-translational modification of histone proteins. Here we confirm a recent report suggesting that nuclear small RNAs are required to initiate or maintain chromatin compaction states in C. elegans germ cells. Additionally, we show that experimentally provided small RNAs are sufficient to direct chromatin compaction and that this compaction requires the small RNA-binding Argonaute NRDE-3, the pre-mRNA associated factor NRDE-2, and the HP1-like protein HPL-2. Our results show that small RNAs, acting via the nuclear RNAi machinery and an HP1-like protein, are capable of driving chromatin compaction in C. elegans.

scholarly journals Caenorhabditis elegans nuclear RNAi factor SET-32 deposits the transgenerational histone modification, H3K23me3

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Lianna Schwartz-Orbach ◽  
Chenzhen Zhang ◽  
Simone Sidoli ◽  
Richa Amin ◽  
Diljeet Kaur ◽  
...  
Keyword(s):  
Chromatin Modification ◽  
Epigenetic Inheritance ◽  
Rnai Pathway ◽  
C Elegans ◽  
And Function ◽  
Nuclear Rnai ◽  
Factor Set

Nuclear RNAi provides a highly tractable system to study RNA-mediated chromatin changes and epigenetic inheritance. Recent studies have indicated that the regulation and function of nuclear RNAi-mediated heterochromatin are highly complex. Our knowledge of histone modifications and the corresponding histonemodifying enzymes involved in the system remains limited. In this study, we show that the heterochromatin mark, H3K23me3, is induced by nuclear RNAi at both exogenous and endogenous targets in C. elegans. In addition, dsRNA-induced H3K23me3 can persist for multiple generations after the dsRNA exposure has stopped. We demonstrate that the histone methyltransferase SET-32, methylates H3K23 in vitro. Both set-32 and the germline nuclear RNAi Argonaute, hrde-1, are required for nuclear RNAi-induced H3K23me3 in vivo. Our data poise H3K23me3 as an additional chromatin modification in the nuclear RNAi pathway and provides the field with a new target for uncovering the role of heterochromatin in transgenerational epigenetic silencing.

scholarly journals The TRIM-NHL protein NHL-2 is a co-factor in the nuclear and somatic RNAi pathways in C. elegans

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Gregory M Davis ◽  
Shikui Tu ◽  
Joshua WT Anderson ◽  
Rhys N Colson ◽  
Menachem J Gunzburg ◽  
...  
Keyword(s):  
Small Rna ◽  
Rna Binding ◽  
Meiotic Chromosome ◽  
Rna Stability ◽  
Rnai Pathway ◽  
Regulatory Pathways ◽  
C Elegans ◽  
Bona Fide ◽  
Rna Pathways ◽  
Nuclear Rnai

Proper regulation of germline gene expression is essential for fertility and maintaining species integrity. In the C. elegans germline, a diverse repertoire of regulatory pathways promote the expression of endogenous germline genes and limit the expression of deleterious transcripts to maintain genome homeostasis. Here we show that the conserved TRIM-NHL protein, NHL-2, plays an essential role in the C. elegans germline, modulating germline chromatin and meiotic chromosome organization. We uncover a role for NHL-2 as a co-factor in both positively (CSR-1) and negatively (HRDE-1) acting germline 22G-small RNA pathways and the somatic nuclear RNAi pathway. Furthermore, we demonstrate that NHL-2 is a bona fide RNA binding protein and, along with RNA-seq data point to a small RNA independent role for NHL-2 in regulating transcripts at the level of RNA stability. Collectively, our data implicate NHL-2 as an essential hub of gene regulatory activity in both the germline and soma.

scholarly journals HERI-1 is a Chromodomain Protein that Negatively Regulates Transgenerational Epigenetic Inheritance

2018 ◽  
Author(s):  
Roberto Perales ◽  
Daniel Pagano ◽  
Gang Wan ◽  
Brandon Fields ◽  
Arneet L. Saltzman ◽  
...  
Keyword(s):  
Gene Silencing ◽  
Epigenetic Inheritance ◽  
Normal Function ◽  
Negative Regulator ◽  
Rnai Pathway ◽  
Transcriptional Gene Silencing ◽  
Direct Role ◽  
Transgenerational Epigenetic Inheritance ◽  
C Elegans ◽  
Nuclear Rnai

AbstractTransgenerational epigenetic inheritance (TEI) is the inheritance of epigenetic information for two or more generations. In most cases, TEI is limited to 2-3 generations. This short-term nature of TEI could be set by innate biochemical limitations to TEI or by genetically encoded systems that actively limit TEI. dsRNA-mediated gene silencing (RNAi) can be inherited in C. elegans (termed RNAi inheritance or RNA-directed TEI). To identify systems that might actively limit RNA-directed TEI, we conducted a forward genetic screen for factors whose mutation enhanced RNAi inheritance. This screen identified the gene heritable enhancer of RNAi (heri-1), whose mutation causes RNAi inheritance to last longer (>20 generations) than normal. heri-1 encodes a protein with a chromodomain and a kinase-homology domain that is expressed in germ cells and localizes to nuclei. In C. elegans, a nuclear branch of the RNAi pathway (nuclear RNAi or NRDE pathway) is required for RNAi inheritance. We find that this NRDE pathway is hyper-responsive to RNAi in heri-1 mutant animals, suggesting that a normal function of HERI-1 is to limit nuclear RNAi and that limiting nuclear RNAi may be the mechanism by which HERI-1 limits RNAi inheritance. Interestingly, we find that HERI-1 binds to genes targeted by RNAi, suggesting that HERI-1 may have a direct role in limiting nuclear RNAi and, therefore, RNAi inheritance. Surprisingly, recruitment of the negative regulator HERI-1 to genes depends upon that same NRDE factors that drive co-transcriptional gene silencing during RNAi inheritance. We therefore speculate that the generational perdurance of RNAi inheritance is set by competing pro- and anti-silencing outputs of the NRDE nuclear RNAi machinery.

scholarly journals A transgenerational role of the germline nuclear RNAi pathway in repressing heat stress-induced transcriptional activation in C. elegans

2016 ◽  
Vol 9 (1) ◽  
Author(s):  
Julie Zhouli Ni ◽  
Natallia Kalinava ◽  
Esteban Chen ◽  
Alex Huang ◽  
Thi Trinh ◽  
...  
Keyword(s):  
Heat Stress ◽  
Transcriptional Activation ◽  
Rnai Pathway ◽  
C Elegans ◽  
Nuclear Rnai

scholarly journals The TRIM-NHL protein NHL-2 is a Novel Co-Factor of the CSR-1 and HRDE-1 22G-RNA Pathways

2018 ◽  
Author(s):  
Gregory M. Davis ◽  
Shikui Tu ◽  
Rhys N. Colson ◽  
Joshua W. T. Anderson ◽  
Menachem J. Gunzburg ◽  
...  
Keyword(s):  
Small Rna ◽  
Rna Binding ◽  
Meiotic Chromosome ◽  
Rna Stability ◽  
Rnai Pathway ◽  
Regulatory Pathways ◽  
C Elegans ◽  
Bona Fide ◽  
Rna Pathways ◽  
Nuclear Rnai

ABSTRACTProper regulation of germline gene expression is essential for fertility and maintaining species integrity. In the C. elegans germline, a diverse repertoire of regulatory pathways promote the expression of endogenous germline genes and limit the expression of deleterious transcripts to maintain genome homeostasis. Here we show that the conserved TRIM-NHL protein, NHL-2, plays an essential role in the C. elegans germline, modulating germline chromatin and meiotic chromosome organization. We uncover a role for NHL-2 as a co-factor in both positively (CSR-1) and negatively (HRDE-1) acting germline 22G-small RNA pathways and the somatic nuclear RNAi pathway. Furthermore, we demonstrate that NHL-2 is a bona fide RNA binding protein and, along with RNA-seq data point to a small RNA independent role for NHL-2 in regulating transcripts at the level of RNA stability. Collectively, our data implicate NHL-2 as an essential hub of gene regulatory activity in both the germline and soma.

scholarly journals CDE-1 suppresses the production of risiRNA by coupling polyuridylation and degradation of 26S rRNA

2019 ◽  
Author(s):  
Yun Wang ◽  
Chenchun Weng ◽  
Xiangyang Chen ◽  
Xufei Zhou ◽  
Xinya Huang ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Caenorhabditis Elegans ◽  
Rnai Pathway ◽  
C Elegans ◽  
26S Rrna ◽  
Nuclear Rnai

AbstractAntisense ribosomal siRNAs (risiRNAs) downregulate pre-rRNAs through the nuclear RNAi pathway in Caenorhabditis elegans. However, the biogenesis and regulation of risiRNAs remain obscure. Previously, we showed that 26S rRNAs are uridylated at the 3’-ends by an unknown terminal polyuridylation polymerase before the rRNAs are degraded by a 3’ to 5’ exoribonuclease SUSI-1(ceDIS3L2). There are three polyuridylation polymerases, CDE-1, PUP-2, and PUP-3, in C. elegans. Here, we found that CDE-1 is specifically involved in suppressing risiRNA production. CDE-1 localizes to perinuclear granules in the germline and uridylates both Argonaute-associated 22G-RNAs and 26S rRNAs at the 3’-ends. Immunoprecipitation followed by mass spectrometry (IP-MS) revealed that CDE-1 interacts with SUSI-1(ceDIS3L2). Consistent with those results, both CDE-1 and SUSI-1(ceDIS3L2) are required for the inheritance of RNAi. Therefore, this work identified a rRNA surveillance machinery of rRNAs that couples terminal polyuridylation and degradation.

scholarly journals C. elegans nuclear RNAi factor SET-32 deposits the transgenerational heritable histone modification, H3K23me3

2020 ◽  
Author(s):  
Lianna Schwartz-Orbach ◽  
Chenzhen Zhang ◽  
Simone Sidoli ◽  
Richa Amin ◽  
Diljeet Kaur ◽  
...  
Keyword(s):  
Chromatin Modification ◽  
Epigenetic Inheritance ◽  
Rnai Pathway ◽  
C Elegans ◽  
Histone Modifying Enzymes ◽  
And Function ◽  
Nuclear Rnai

AbstractNuclear RNAi provides a highly tractable system to study RNA-mediated chromatin changes and epigenetic inheritance. Recent studies have indicated that the regulation and function of nuclear RNAi-mediated heterochromatin are highly complex. Our knowledge of histone modifications and the corresponding histone modifying enzymes involved in the system remains limited. In this study, we show that the heterochromatin mark, H3K23me3, is induced by nuclear RNAi at both exogenous and endogenous targets in C. elegans. In addition, dsRNA-induced H3K23me3 can be inherited for four generations. We demonstrate that the histone methyltransferase SET-32, methylates H3K23 in vitro. Both set-32 and the germline nuclear RNAi Argonaute, hrde-1, are required for nuclear RNAi-induced H3K23me3 in vivo. Our data poise H3K23me3 as an additional chromatin modification in the nuclear RNAi pathway and provides the field with a new target for uncovering the role of heterochromatin in transgenerational epigenetic silencing.

scholarly journals Somatic aging pathways regulate reproductive plasticity in Caenorhabditis elegans

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Maria C Ow ◽  
Alexandra M Nichitean ◽  
Sarah E Hall
Keyword(s):  
Gene Expression ◽  
Larval Stage ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Rnai Pathway ◽  
C Elegans ◽  
Fat Stores ◽  
Functional Germline ◽  
Nuclear Rnai

In animals, early-life stress can result in programmed changes in gene expression that can affect their adult phenotype. In C. elegans nematodes, starvation during the first larval stage promotes entry into a stress-resistant dauer stage until environmental conditions improve. Adults that have experienced dauer (postdauers) retain a memory of early-life starvation that results in gene expression changes and reduced fecundity. Here we show that the endocrine pathways attributed to the regulation of somatic aging in C. elegans adults lacking a functional germline also regulate the reproductive phenotypes of postdauer adults that experienced early-life starvation. We demonstrate that postdauer adults reallocate fat to benefit progeny at the expense of the parental somatic fat reservoir and exhibit increased longevity compared to controls. Our results also show that the modification of somatic fat stores due to parental starvation memory is inherited in the F1 generation and may be the result of crosstalk between somatic and reproductive tissues mediated by the germline nuclear RNAi pathway.

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