C. elegans germ granules require both assembly and localized regulators for mRNA repression

Aoki, Scott T.; Lynch, Tina R.; Crittenden, Sarah L.; Bingman, C.A.; Wickens, Marvin; Kimble, Judith

doi:10.1038/s41467-021-21278-1

Cited by 37 publications

(34 citation statements)

References 81 publications

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“…P granules exhibit similar permeability properties and have been proposed to function as extensions of the nucleopore environment (Updike et al, 2011). PGL proteins contain two dimerization domains and RNA-binding RGG domains (Aoki et al, 2016(Aoki et al, , 2021. Purified PGL-3 forms condensates in vitro in a manner that is stimulated by RNA, consistent with the apparent RNA requirement for P granule integrity in vivo (Saha et al, 2016;Putnam et al, 2019).…”

Section: Liquid-like Properties Of Nuage Condensatesmentioning

confidence: 53%

Nuage condensates: accelerators or circuit breakers for sRNA silencing pathways?

Ouyang

Seydoux

2021

RNA

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Nuage are RNA-rich condensates that assemble around the nuclei of developing germ cells. Many proteins required for the biogenesis and function of silencing small RNAs (sRNAs) enrich in nuage, and it is often assumed that nuage is the cellular site where sRNAs are synthesized and encounter target transcripts for silencing. Using C. elegans as a model, we examine the complex multi-condensate architecture of nuage and review evidence for compartmentalization of silencing pathways. We consider the possibility that nuage condensates balance the activity of competing sRNA pathways and serve to limit, rather than enhance, sRNA amplification to protect transcripts from dangerous run-away silencing.

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Section: Liquid-like Properties Of Nuage Condensatesmentioning

confidence: 53%

Nuage condensates: accelerators or circuit breakers for sRNA silencing pathways?

Ouyang

Seydoux

2021

RNA

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“…Our data showed that OMA-1 and OMA-1 P240L were less localized to P granules after introducing mutations in APC/C genes (Figures 4, 5). Previous studies suggested during early embryogenesis, untranslated maternal mRNAs are enriched in P granules and are released from P granules at specific developmental stages to exhibit corresponding functions (Spike et al, 2014;Lee et al, 2020;Parker et al, 2020;Aoki et al, 2021). Since we and others also found OMA-1 is enriched in P granules in 1-, 2-, and 4-cell stage embryos, considering OMA-1 binds to 3 UTR to repress translation of maternal mRNAs, it is reasonable to suggest that OMA-1 and its cognate mRNAs are associated with each other in P granules, and delocalization of OMA-1 from P granules indicates disassociation of OMA-1 from its cognate mRNAs (Figure 7).…”

Section: Discussionmentioning

confidence: 99%

The APC/CFZY–1/Cdc20 Complex Coordinates With OMA-1 to Regulate the Oocyte-to-Embryo Transition in Caenorhabditis elegans

et al. 2021

Front. Cell Dev. Biol.

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During oocyte maturation and the oocyte-to-embryo transition, key developmental regulators such as RNA-binding proteins coordinate translation of particular messenger RNA (mRNAs) and related developmental processes by binding to their cognate maternal mRNAs. In the nematode Caenorhabditis elegans, these processes are regulated by a set of CCCH zinc finger proteins. Oocyte maturation defective-1 (OMA-1) and OMA-2 are two functionally redundant CCCH zinc finger proteins that turnover rapidly during the first embryonic cell division. These turnovers are required for proper transition from oogenesis to embryogenesis. A gain-of-function mutant of OMA-1, oma-1(zu405), stabilizes and delays degradation of OMA-1, resulting in delayed turnover and mis-segregation of other cell fate determinants, which eventually causes embryonic lethality. We performed a large-scale forward genetic screen to identify suppressors of the oma-1(zu405) mutant. We show here that multiple alleles affecting functions of various anaphase promoting complex/cyclosome (APC/C) subunits, including MAT-1, MAT-2, MAT-3, EMB-30, and FZY-1, suppress the gain-of-function mutant of OMA-1. Transcriptome analysis suggested that overall transcription in early embryos occurred after introducing mutations in APC/C genes into the oma-1(zu405) mutant. Mutations in APC/C genes prevent OMA-1 enrichment in P granules and correct delayed degradation of downstream cell fate determinants including pharynx and intestine in excess-1 (PIE-1), posterior segregation-1 (POS-1), muscle excess-3 (MEX-3), and maternal effect germ-cell defective-1 (MEG-1). We demonstrated that only the activator FZY-1, but not FZR-1, is incorporated in the APC/C complex to regulate the oocyte-to-embryo transition. Our findings suggested a genetic relationship linking the APC/C complex and OMA-1, and support a model in which the APC/C complex promotes P granule accumulation and modifies RNA binding of OMA-1 to regulate the oocyte-to-embryo transition process.

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“…It is the first method to identify stress granule RNAs in single cells and in tissues, and could be particularly important to reveal heterogeneity between cells, within primary cells or tissues in their response to different stress. Importantly, this method could also allow the identification the RNA content of other RNA based phase separated assemblies, whether formed upon stress or existing in basal conditions, such as neuronal granules (63,64), posterior granules in Drosophila oocyte (65,66) and P granules in C.elegans (67,68), whose RNA content has so far been difficult to isolate and study.…”

Section: Discussionmentioning

confidence: 99%

Identification of the stress granule transcriptome via RNA-editing in single cells andin vivo

VanInsberghe

Battich

et al. 2021

Preprint

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Stress granules are phase separated assemblies formed around mRNAs whose identities remain elusive. The techniques available to identify the RNA content of stress granules rely on their physical purification, and are therefore not suitable for single cells and tissues displaying cell heterogeneity. Here, we adapted TRIBE (Target of RNA-binding proteins Identified by Editing) to detect stress granule RNAs by fusing a stress granule RNA-binding protein (FMR1) to the catalytic domain of an RNA-editing enzyme (ADAR). RNAs colocalized with this fusion are edited, producing mutations that are detectable by sequencing. We first optimized the expression of this fusion protein so that RNA editing preferentially occurs in stress granules. We then show that this purification-free method can reliably identify stress granule RNAs in bulk and single S2 cells, and in Drosophila tissues, such as 398 neuronal stress granule mRNAs encoding ATP binding, cell cycle and transcription factors. This new method opens the possibility to identify the RNA content of stress granules as well other RNA based assemblies in single cells derived from tissues.

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C. elegans germ granules require both assembly and localized regulators for mRNA repression

Cited by 37 publications

References 81 publications

Nuage condensates: accelerators or circuit breakers for sRNA silencing pathways?

Nuage condensates: accelerators or circuit breakers for sRNA silencing pathways?

The APC/CFZY–1/Cdc20 Complex Coordinates With OMA-1 to Regulate the Oocyte-to-Embryo Transition in Caenorhabditis elegans

Identification of the stress granule transcriptome via RNA-editing in single cells andin vivo

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