Translational Control in the Caenorhabditis elegans Germ Line

Nousch, Marco; Eckmann, Christian R.

doi:10.1007/978-1-4614-4015-4_8

Cited by 52 publications

(60 citation statements)

References 175 publications

(220 reference statements)

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“…The deletion of a non-essential deadenylase in Drosophila resulted in gametogenesis defects (Morris et al, 2005). A similar observation was made for another deadenylase in mice (Nakamura et al, 2004), suggesting that deadenylases in general could have important functions in germ cell development (Nousch and Eckmann, 2013). Over recent years, the nematode model organism C. elegans became a paradigm for studying mRNA regulation in connection with germ cell development.…”

Section: Introductionmentioning

confidence: 66%

The Ccr4-Not deadenylase complex constitutes the major poly(A) removal activity inC. elegans

Nousch

Techritz

Hampel

et al. 2013

Journal of Cell Science

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SummaryPost-transcriptional regulatory mechanisms are widely used to control gene expression programs of tissue development and physiology. Controlled 39 poly(A) tail-length changes of mRNAs provide a mechanistic basis of such regulation, affecting mRNA stability and translational competence. Deadenylases are a conserved class of enzymes that facilitate poly(A) tail removal, and their biochemical activities have been mainly studied in the context of single-cell systems. Little is known about the different deadenylases and their biological role in multicellular organisms. In this study, we identify and characterize all known deadenylases of Caenorhabditis elegans, and identify the germ line as tissue that depends strongly on deadenylase activity. Most deadenylases are required for hermaphrodite fertility, albeit to different degrees. Whereas ccr-4 and ccf-1 deadenylases promote germline function under physiological conditions, panl-2 and parn-1 deadenylases are only required under heat-stress conditions. We also show that the Ccr4-Not core complex in nematodes is composed of the two catalytic subunits CCR-4 and CCF-1 and the structural subunit NTL-1, which we find to regulate the stability of CCF-1. Using bulk poly(A) tail measurements with nucleotide resolution, we detect strong deadenylation defects of mRNAs at the global level only in the absence of ccr-4, ccf-1 and ntl-1, but not of panl-2, parn-1 and parn-2. Taken together, this study suggests that the Ccr4-Not complex is the main deadenylase complex in C. elegans germ cells. On the basis of this and as a result of evidence in flies, we propose that the conserved Ccr4-Not complex is an essential component in post-transcriptional regulatory networks promoting animal reproduction.

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Section: Introductionmentioning

confidence: 66%

The Ccr4-Not deadenylase complex constitutes the major poly(A) removal activity inC. elegans

Nousch

Techritz

Hampel

et al. 2013

Journal of Cell Science

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“…Much has been described about mRNA repression by RNA-binding proteins (e.g. GLD-1, FBFs, OMA-1, CPEB, Nanos and Pumilio) and how they are vital for germ cell development (reviewed in Friday and Keiper, 2015;Lee et al, 2015;Mendez and Richter, 2001;Nousch and Eckmann, 2013;Parisi and Lin, 2000). Repression, however, represents only the first half of the regulation.…”

Section: Discussionmentioning

confidence: 99%

Spatial and temporal translational control of germ cell mRNAs mediated by the eIF4E isoform IFE-1

Friday

Henderson

Morrison

et al. 2015

Journal of Cell Science

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Regulated mRNA translation is vital for germ cells to produce new proteins in the spatial and temporal patterns that drive gamete development. Translational control involves the de-repression of stored mRNAs and their recruitment by eukaryotic initiation factors (eIFs) to ribosomes. C. elegans expresses five eIF4Es (IFE-1-IFE-5); several have been shown to selectively recruit unique pools of mRNA. Individual IFE knockouts yield unique phenotypes due to inefficient translation of certain mRNAs. Here, we identified mRNAs preferentially translated through the germline-specific eIF4E isoform IFE-1. Differential polysome microarray analysis identified 77 mRNAs recruited by IFE-1. Among the IFE-1-dependent mRNAs are several required for late germ cell differentiation and maturation. Polysome association of gld-1, vab-1, vpr-1, rab-7 and rnp-3 mRNAs relies on IFE-1. Live animal imaging showed IFE-1-dependent selectivity in spatial and temporal translation of germline mRNAs. Altered MAPK activation in oocytes suggests dual roles for IFE-1, both promoting and suppressing oocyte maturation at different stages. This single eIF4E isoform exerts positive, selective translational control during germ cell differentiation.

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“…How gld-3 might act to repress GLD-1 base levels is unclear. GLD-3 may repress GLD-1 indirectly by facilitating binding by direct repressors, such as FBF, based on its proposed function as an RNA-protein scaffold (Nousch and Eckmann 2013).…”

Section: Gld-1 Levels In Germ Cells Irreversibly Committed To Meioticmentioning

confidence: 99%

Germline Stem Cell Differentiation Entails Regional Control of Cell Fate Regulator GLD-1 in Caenorhabditis elegans

2016

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Germline stem cell differentiation in Caenorhabditis elegans is controlled by glp-1 Notch signaling. Cell fate regulator GLD-1 is sufficient to induce meiotic entry and expressed at a high level during meiotic prophase, inhibiting mitotic gene activity. glp-1 signaling and other regulators control GLD-1 levels post-transcriptionally (low in stem cells, high in meiotic prophase), but many aspects of GLD-1 regulation are uncharacterized, including the link between glp-1-mediated transcriptional control and post-transcriptional GLD-1 regulation. We established a sensitive assay to quantify GLD-1 levels across an 35-cell diameter field, where distal germline stem cells differentiate proximally into meiotic prophase cells in the adult C. elegans hermaphrodite, and applied the approach to mutants in known or proposed GLD-1 regulators. In wild-type GLD-1 levels elevated 20-fold in a sigmoidal pattern. We found that two direct transcriptional targets of glp-1 signaling, lst-1 and sygl-1, were individually required for repression of GLD-1. We determined that lst-1 and sygl-1 act in the same genetic pathway as known GLD-1 translational repressor fbf-1, while lst-1 also acts in parallel to fbf-1, linking glp-1-mediated transcriptional control and post-transcriptional GLD-1 repression. Additionally, we estimated the position in wild-type gonads where germ cells irreversibly commit to meiotic development based on GLD-1 levels in worms where glp-1 activity was manipulated to cause an irreversible fate switch. Analysis of known repressors and activators, as well as modeling the sigmoidal accumulation pattern, indicated that regulation of GLD-1 levels is largely regional, which we integrated with the current view of germline stem cell differentiation.

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Translational Control in the Caenorhabditis elegans Germ Line

Cited by 52 publications

References 175 publications

The Ccr4-Not deadenylase complex constitutes the major poly(A) removal activity inC. elegans

The Ccr4-Not deadenylase complex constitutes the major poly(A) removal activity inC. elegans

Spatial and temporal translational control of germ cell mRNAs mediated by the eIF4E isoform IFE-1

Germline Stem Cell Differentiation Entails Regional Control of Cell Fate Regulator GLD-1 in Caenorhabditis elegans

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