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Adequate dietary intake of essential metals such as zinc is important for maintaining homeostasis. Abnormal zinc intake in Caenorhabditis elegans has been shown to increase or decrease normal lifespan by influencing the insulin/IGF-1 pathway. Distribution of zinc is achieved by a family of highly conserved zinc transport proteins (ZIPT in C. elegans). This study investigated the role of the zipt family of genes and showed that depletion of individual zipt genes results in a decreased lifespan. Moreover, zipt-16 and zipt-17 mutants synthetically interact with the insulin/IGF cofactors daf-16 and skn-1, and cause abnormal localisation of DAF-16. This study suggests that the zipt family of genes are required for maintaining normal lifespan through influencing the insulin/IGF-1 pathway., (© 2019 Federation of European Biochemical Societies.)

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., Competing Interests: GD, ST, JA, RC, MG, MF, DR, SS, JS, US, RL, TM, MW, KM, QM, TH, JW, JC, ZW, PB No competing interests declared

TRIM-NHL proteins are highly conserved regulators of developmental pathways in vertebrates and invertebrates. The TRIM-NHL family member NHL-2 in Caenorhabditis elegans functions as a miRNA cofactor to regulate developmental timing. Similar regulatory roles have been reported in other model systems, with the mammalian ortholog in mice, TRIM32, contributing to muscle and neuronal cell proliferation via miRNA activity. Given the interest associated with TRIM-NHL family proteins, we aimed to further investigate the role of NHL-2 in C. elegans development by using a synthetic RNAi screening approach. Using the ORFeome library, we knocked down 11,942 genes in wild-type animals and nhl-2 null mutants. In total, we identified 42 genes that produced strong reproductive synthetic phenotypes when knocked down in nhl-2 null mutants, with little or no change when knocked down in wild-type animals. These included genes associated with transcriptional processes, chromosomal integrity, and key cofactors of the germline small 22G RNA pathway., (Copyright © 2017 Davis et al.)

An extended meiotic prophase is a hallmark of oogenesis. Hormonal signaling activates the CDK1/cyclin B kinase to promote oocyte meiotic maturation, which involves nuclear and cytoplasmic events. Nuclear maturation encompasses nuclear envelope breakdown, meiotic spindle assembly, and chromosome segregation. Cytoplasmic maturation involves major changes in oocyte protein translation and cytoplasmic organelles and is poorly understood. In the nematode Caenorhabditis elegans , sperm release the major sperm protein (MSP) hormone to promote oocyte growth and meiotic maturation. Large translational regulatory ribonucleoprotein (RNP) complexes containing the RNA-binding proteins OMA-1, OMA-2, and LIN-41 regulate meiotic maturation downstream of MSP signaling. To understand the control of translation during meiotic maturation, we purified LIN-41-containing RNPs and characterized their protein and RNA components. Protein constituents of LIN-41 RNPs include essential RNA-binding proteins, the GLD-2 cytoplasmic poly(A) polymerase, the CCR4-NOT deadenylase complex, and translation initiation factors. RNA sequencing defined messenger RNAs (mRNAs) associated with both LIN-41 and OMA-1, as well as sets of mRNAs associated with either LIN-41 or OMA-1 Genetic and genomic evidence suggests that GLD-2, which is a component of LIN-41 RNPs, stimulates the efficient translation of many LIN-41-associated transcripts. We analyzed the translational regulation of two transcripts specifically associated with LIN-41 which encode the RNA regulators SPN-4 and MEG-1 We found that LIN-41 represses translation of spn-4 and meg-1 , whereas OMA-1 and OMA-2 promote their expression. Upon their synthesis, SPN-4 and MEG-1 assemble into LIN-41 RNPs prior to their functions in the embryo. This study defines a translational repression-to-activation switch as a key element of cytoplasmic maturation., (Copyright © 2017 by the Genetics Society of America.)

TRIM-NHL proteins represent a large class of metazoan proteins implicated in development and disease. We demonstrate that a C. elegans TRIM-NHL protein, NHL-2, functions as a cofactor for the microRNA-induced silencing complex (miRISC) and thereby enhances the posttranscriptional repression of several genetically verified microRNA targets, including hbl-1 and let-60/Ras (by the let-7 family of microRNAs) and cog-1 (by the lsy-6 microRNA). NHL-2 is localized to cytoplasmic P-bodies and physically associates with the P-body protein CGH-1 and the core miRISC components ALG-1/2 and AIN-1. nhl-2 and cgh-1 mutations compromise the repression of microRNA targets in vivo but do not affect microRNA biogenesis, indicating a role for an NHL-2:CGH-1 complex in the effector phase of miRISC activity. We propose that the NHL-2:CGH-1 complex functions in association with mature miRISC to modulate the efficacy of microRNA:target interactions in response to physiological and developmental signals, thereby ensuring the robustness of genetic regulatory pathways regulated by microRNAs.

Germ cells use both positive and negative mRNA translational control to regulate gene expression that drives their differentiation into gametes. mRNA translational control is mediated by RNA-binding proteins, miRNAs, and translation initiation factors. We have uncovered the discrete roles of two translation initiation factor eIF4E isoforms (IFE-1 and -3) that bind m7GTP mRNA caps during C. elegans germline development. IFE-3 plays important roles in germline sex determination (GSD), where it promotes oocyte cell fate and is dispensable for spermatogenesis. IFE-3 is expressed throughout the germline, localizes to germ granules but distinct from IFE-1 and PGL-1, and facilitates oocyte growth and viability. This contrasts with the robust expression of IFE-1 in spermatocytes, the isoform that resides within P granules in spermatocytes and oocytes, and promotes late spermatogenesis. Each eIF4E is localized by its cognate eIF4E binding protein (IFE-1:PGL-1 and IFE-3:IFET-1). IFE-3 and IFET-1 regulate translation of several GSD mRNAs, but not those under control of IFE-1. Distinct mutant phenotypes, in vivo localization, and differential mRNA translation suggest independent dormant and active periods for each eIF4E isoform in the germline. [ABSTRACT FROM AUTHOR]

Germ granules are an evolutionarily conserved feature of germ cell cytoplasm and are critical for gametogenesis and embryonic development. Germ granules are highly enriched for RNA and RNA-binding proteins and are key centers for post-transcriptional gene regulation in germ cells. Over the last 20 years, the molecular events in germ granule function and formation in several organisms have begun to be revealed. This review seeks to give an overview of some conserved features of germ granules and highlights a conserved strategy for regulating translation of maternal mRNAs. © 2012 IUBMB IUBMB Life, 64(7): 586-594, 2012 [ABSTRACT FROM AUTHOR]

The article discusses the study "A Conserved RNA-Protein Complex Component Involved in Physiological Germline Apoptosis Regulation in C. Elegans," by Peter R. Boag, Akira Nakamura and T. Keith Blackwell. The study focused on a predicted RNA-binding protein, CAR-1, that associates with CGH-1 and Y-box proteins within a conserved germline RNA-protein complex, and in cytoplasmic particles in the gonad and early embryo. It proposed that the cell death pathway facilitates the formation of functional oocytes.