A Small-RNA-Mediated Feedback Loop Maintains Proper Levels of 22G-RNAs in C. elegans

Rogers, Alicia K.; Phillips, Carolyn M.

doi:10.1016/j.celrep.2020.108279

Cited by 12 publications

(18 citation statements)

References 55 publications

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“…[ 63 , 66 , 85 ] A GFP::NRDE-3 transgene, which localizes from the nucleus to the cytoplasm upon disruption of the 26G-RNA pathway, [ 63 , 86 ] remained expressed in the nucleus when crossed into lotr-1 mutants ( S4F Fig ), indicating the 26G-RNA pathway is not critically impaired. It has been recently reported that deregulation of mutator-dependent 22G-RNAs targeting the eri-6/7 locus may destabilize ERI-6/7, a protein required for ERGO-1-dependent 22G-RNA biogenesis [ 87 ]. In l otr-1 mutants, we find a mild increase of 22G-RNAs in this locus ( S4G Fig ), which may explain the lower levels of ERGO-1-dependent 26G-RNAs ( Fig 4A ).…”

Section: Resultsmentioning

confidence: 99%

The Caenorhabditis elegans TDRD5/7-like protein, LOTR-1, interacts with the helicase ZNFX-1 to balance epigenetic signals in the germline

et al. 2022

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LOTUS and Tudor domain containing proteins have critical roles in the germline. Proteins that contain these domains, such as Tejas/Tapas in Drosophila, help localize the Vasa helicase to the germ granules and facilitate piRNA-mediated transposon silencing. The homologous proteins in mammals, TDRD5 and TDRD7, are required during spermiogenesis. Until now, proteins containing both LOTUS and Tudor domains in Caenorhabditis elegans have remained elusive. Here we describe LOTR-1 (D1081.7), which derives its name from its LOTUS and Tudor domains. Interestingly, LOTR-1 docks next to P granules to colocalize with the broadly conserved Z-granule helicase, ZNFX-1. The Tudor domain of LOTR-1 is required for its Z-granule retention. Like znfx-1 mutants, lotr-1 mutants lose small RNAs from the 3’ ends of WAGO and mutator targets, reminiscent of the loss of piRNAs from the 3’ ends of piRNA precursor transcripts in mouse Tdrd5 mutants. Our work shows that LOTR-1 acts with ZNFX-1 to bring small RNA amplifying mechanisms towards the 3’ ends of its RNA templates.

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Section: Resultsmentioning

confidence: 99%

The Caenorhabditis elegans TDRD5/7-like protein, LOTR-1, interacts with the helicase ZNFX-1 to balance epigenetic signals in the germline

et al. 2022

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“…In addition, the gradual down-regulation of several miRNAs from parents to children; recall a gene silencing booster (amplification siRNAs) reported in a model system such as plant, mouse or C. elegans 36 with the exception in mammals of the RDRP gene /or activity have yet to be identified. Other mechanisms for persistence of siRNAs are proposed/ or should be identified.…”

Section: Inheritance In Autismmentioning

confidence: 99%

Progressive decline in the levels of six miRNAs from parents to children in autism

Rassoulzadegan

Mehmetbeyoglu

Yılmaz

et al. 2022

Preprint

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SummaryThe growing burden of a gradual increase in births of children with autism has placed it at the center of the concerns of major laboratories. We have previously detected a decrease in the levels of six miRNAs (miR-19a-3p, miR-361-5p, miR-3613-3p, miR-150-5p, miR-126-3p, and miR-499a-5p) in parents and their children inherited at a lower level. Here, we suggest that down-regulation of each of these six miRNAs inherited from parents contributes to the development of children with autism. We compare their levels of distribution in each family between the autistic child and siblings. We find that the distribution of levels of these miRNAs in siblings (undiagnosed as autism) is not always higher than in autistic children, but it is at varying levels. These data support a model in which autistic behavior relies on low levels of the six miRNAs expressed in children potentially associated with autistic syndrome (ASD). The intimate link between miRNAs levels and behavioral characteristics suggests possibilities for understanding the basic circuitry involved in autism and thus advancing partial knowledge of brain functions. An early diagnosis of autism helps provide children an environment conducive to their development.Graphical abstract

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“…Similar mechanism was described for other conditions (or mutants) where worms exhibit an enhanced RNAi phenotype ( Duchaine et al., 2006 ; Houri-Ze'evi et al., 2016 ; Lev et al., 2017 ). Recently an eri-6/7- based feedback between MUT-16 and ERGO-1 small RNA pathways ( Rogers and Phillips, 2020b ) was described. It is possible that similar feedback mechanism between different small RNA pathways may also be involved in these inheritance patterns.…”

Section: Germ Granules Regulate the Inheritance Of Small Rnasmentioning

confidence: 99%

Germ Granules Allow Transmission of Small RNA-Based Parental Responses in the “Germ Plasm”

Lev

Rechavi

2020

iScience

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Summary In the recent decade small RNA-based inheritance has been implicated in a variety of transmitted physiological responses to the environment. In Caenorhabditis elegans , heritable small RNAs rely on RNA-dependent RNA polymerases, RNA-processing machinery, chromatin modifiers, and argonauts for their biogenesis and gene-regulatory effects. Importantly, many of these factors reside in evolutionary conserved germ granules that are required for maintaining germ cell identity and gene expression. Recent literature demonstrated that transient disturbance to the stability of the germ granules leads to changes in the pools of heritable small RNAs and the physiology of the progeny. In this piece, we discuss the heritable consequences of transient destabilization of germ granules and elaborate on the various small RNA-related processes that act in the germ granules. We further propose that germ granules may serve as environment sensors that translate environmental changes to inheritable small RNA-based responses.

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A Small-RNA-Mediated Feedback Loop Maintains Proper Levels of 22G-RNAs in C. elegans

Cited by 12 publications

References 55 publications

The Caenorhabditis elegans TDRD5/7-like protein, LOTR-1, interacts with the helicase ZNFX-1 to balance epigenetic signals in the germline

The Caenorhabditis elegans TDRD5/7-like protein, LOTR-1, interacts with the helicase ZNFX-1 to balance epigenetic signals in the germline

Progressive decline in the levels of six miRNAs from parents to children in autism

Germ Granules Allow Transmission of Small RNA-Based Parental Responses in the “Germ Plasm”

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