Germline Maintenance Through the Multifaceted Activities of GLH/Vasa in<i>Caenorhabditis elegans</i>P Granules

Marnik, Elisabeth A.; Fuqua, J. Heath; Sharp, Catherine S.; Rochester, Jesse D.; Xu, Emily; Holbrook, Sarah E.; Updike, Dustin L.

doi:10.1534/genetics.119.302670

Cited by 46 publications

(53 citation statements)

References 57 publications

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“…This non-spherical appearance of P granules due to association with nuclear pores has been described as a "wetting" of the nuclear membrane (Brangwynne et al 2009). Interestingly, a mutation in GLH-1 also creates large, round P granules, possibly caused by an inability to release captured RNA (Marnik et al 2019). As first proposed by Sheth et al (2010), our data suggests that P granule association with the nuclear periphery may also depend on the sustained presence of transcripts exiting the nucleus.…”

Section: Regulation Of Mutator Foci By Rnasupporting

confidence: 73%

“…We also noticed that P granules became more rounded at three hours post-transcriptional inhibition in late pachytene compared to mid pachytene. Typically, P granules are intimately associated with nuclear pores, likely through the interaction of the FG-repeats in DEAD-box helicases GLH-1, GLH-2, and GLH-4, with nuclear pore-containing FG-repeat proteins (Updike et al 2011;Marnik et al 2019). This non-spherical appearance of P granules due to association with nuclear pores has been described as a "wetting" of the nuclear membrane (Brangwynne et al 2009).…”

Section: Regulation Of Mutator Foci By Rnamentioning

confidence: 99%

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Mutator Foci Are Regulated by Developmental Stage, RNA, and the Germline Cell Cycle in Caenorhabditis elegans

Uebel¹,

Agbede²,

Wallis³

et al. 2020

G3 Genes|Genomes|Genetics

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RNA interference is a crucial gene regulatory mechanism in Caenorhabditis elegans. Phase-separated perinuclear germline compartments called Mutator foci are a key element of RNAi, ensuring robust gene silencing and transgenerational epigenetic inheritance. Despite their importance, Mutator foci regulation is not well understood, and observations of Mutator foci have been largely limited to adult hermaphrodite germlines. Here we reveal that punctate Mutator foci arise in the progenitor germ cells of early embryos and persist throughout all larval stages. They are additionally present throughout the male germline and in the cytoplasm of post-meiotic spermatids, suggestive of a role in paternal epigenetic inheritance. In the adult germline, transcriptional inhibition results in a pachytene-specific loss of Mutator foci, indicating that Mutator foci are partially reliant on RNA for their stability. Finally, we demonstrate that Mutator foci intensity is modulated by the stage of the germline cell cycle and specifically, that Mutator foci are brightest and most robust in the mitotic cells, transition zone, and late pachytene of adult germlines. Thus, our data defines several new factors that modulate Mutator foci morphology which may ultimately have implications for efficacy of RNAi in certain cell stages or environments.

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Section: Regulation Of Mutator Foci By Rnasupporting

confidence: 73%

Section: Regulation Of Mutator Foci By Rnamentioning

confidence: 99%

Mutator Foci Are Regulated by Developmental Stage, RNA, and the Germline Cell Cycle in Caenorhabditis elegans

Uebel¹,

Agbede²,

Wallis³

et al. 2020

G3 Genes|Genomes|Genetics

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show abstract

“…Figure S3). Each transgene was also crossed into a pgl1-1::RFP reporter background and homozygous strains were established ( Figure S4) (Marnik et al, 2019).…”

Section: Transgenic Nematode Productionmentioning

confidence: 99%

A long lost key opens an ancient lock: Drosophila Myb causes a synthetic multivulval phenotype in nematodes

et al. 2020

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The five-protein MuvB core complex is highly conserved in animals. This nuclear complex interacts with RB family tumor suppressor proteins and E2F-DP transcription factors to form DREAM complexes that repress genes that regulate cell cycle progression and cell fate. The MuvB core complex also interacts with proteins Myb family oncoproteins to form the Myb-MuvB complexes that activate many of the same genes. We show that animaltype Myb genes are present in Bilateria, Cnidaria, and Placozoa, the latter including the simplest known animal species. However, bilaterian nematode worms lost their animal-type Myb genes hundreds of millions of years ago. Nevertheless, amino acids in the LIN9 and LIN52 proteins that directly interact with the MuvB-binding domains of human B-Myb and Drosophila Myb are conserved in C. elegans. Here we show that, despite greater than 500 million years since their last common ancestor, the Drosophila melanogaster Myb protein can bind to the nematode LIN9-LIN52 proteins in vitro and can cause a synthetic multivulval (synMuv) phenotype in vivo. This phenotype is similar to that caused by loss-of-function mutations in C. elegans synMuvB class genes including those that encode homologs of the MuvB core, RB, E2F, and DP. Furthermore, amino acid substitutions in the MuvB-binding domain of Drosophila Myb that disrupt its functions in vitro and in vivo also disrupt these activities in C. elegans. We speculate that nematodes and other animals may contain another protein that can bind to LIN9 and LIN52 in order to activate transcription of genes repressed by DREAM complexes.

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“…[72,77,78] In C. elegans, there are two partially redundant Vasa homologs, GLH-1 and GLH-2. [79] Single mutations in either GLH are temperature-sensitive sterile, while double mutants are sterile at all temperatures. Brood size and fertility are minimally impacted in all lotr-1 mutants at both 20°C and the first generation shifted to 26°C (Fig 3A).…”

Section: Functional Analysis Of Lotr-1 Domains Reveals Effects On Subcellular Localization and Fertilitymentioning

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. 2021

Preprint

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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 Vasa 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. LOTR-1's Z-granule association requires its Tudor domain, but both LOTUS and Tudor deletions affect brood size when coupled with a knockdown of the Vasa homolog glh-1. In addition to interacting with the germ-granule components WAGO-1, PRG-1 and DEPS-1, we identified a Tudor-dependent association with ZNFX-1. 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 suggests that LOTR-1 acts in a conserved mechanism that brings small RNA generating mechanisms towards the 3' ends of small RNA templates or precursors.

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Germline Maintenance Through the Multifaceted Activities of GLH/Vasa inCaenorhabditis elegansP Granules

Abstract: Vasa homologs are ATP-dependent DEAD-box helicases, multipotency factors, and critical components that specify and protect the germline. They regulate translation, amplify piRNAs, and act as RNA solvents; but, the limited availability of mutagenesis-derived alleles and their wide...

Cited by 46 publications

References 57 publications

Mutator Foci Are Regulated by Developmental Stage, RNA, and the Germline Cell Cycle in Caenorhabditis elegans

Mutator Foci Are Regulated by Developmental Stage, RNA, and the Germline Cell Cycle in Caenorhabditis elegans

A long lost key opens an ancient lock: Drosophila Myb causes a synthetic multivulval phenotype in nematodes

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

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