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Parasitol Today,
1996]
Historically, peptidergic substances (in the form of neurosecretions) were linked to moulting in nematodes. More recently, there has been a renewal of interest in nematode neurobiology, initially triggered by studies demonstrating the localization of peptide immunoreactivities to the nervous system. Here, David Brownlee, Ian Fairweather, Lindy Holden-Dye and Robert Walker will review progress on the isolation of nematode neuropeptides and efforts to unravel their physiological actions and inactivation mechanisms. Future avenues for research are suggested and the potential exploitation of peptidergic pathways in future therapeutic strategies
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J Mol Biol,
2015]
Maf1 was first identified in yeast, and studies in metazoans have primarily focused on examining its role in the repression of transcription that is dependent on RNA polymerase III. Recent work has revealed a novel and conserved function for Maf1 in the maintenance of intracellular lipid pools in Caenorhabditis elegans, mice, and cancer cell lines. Although additional Maf1 targets are likely, they have not been identified, and these recent findings begin to define specific activities for Maf1 in multicellular organisms beyond the regulation of RNA polymerase III transcription and suggest that Maf1 plays a more diverse role in organismal physiology. We will discuss these newly defined physiological roles of Maf1 that point to its placement as an important new player in lipid metabolism with implications in human metabolic diseases such as obesity and cancer, which display prominent defects in lipid homeostasis.
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Cell,
2001]
In 1998, The C. elegans Sequencing Consortium (1998) announced the essentially complete Caenorhabditis elegans genomic sequence, setting a high standard for sequencing multicellular genomes. As of April 2001, the C. elegans genome, including repetitive regions, is >99.6% complete with sequence equivalent to what many genome projects call phase III. How has this changed the lives of C. elegans researchers, and our view of the worm?
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Dev Dyn,
2010]
We review recent studies that have advanced our understanding of the molecular mechanisms regulating transcription in the nematode C. elegans. Topics covered include: (i) general properties of C. elegans promoters; (ii) transcription factors and transcription factor combinations involved in cell fate specification and cell differentiation; (iii) new roles for general transcription factors; (iv) nucleosome positioning in C. elegans "chromatin"; and (v) some characteristics of histone variants and histone modifications and their possible roles in controlling C. elegans transcription.
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Biochim Biophys Acta,
2018]
As a master regulator of transcription by RNA polymerase (Pol) III, Maf1 represses the synthesis of highly abundant non-coding RNAs as anabolic signals dissipate, as the quality or quantity of nutrients decreases, and under a wide range of cellular and environmental stress conditions. Thus, Maf1 responds to changes in cell physiology to conserve metabolic energy and to help maintain appropriate levels of tRNAs and other essential non-coding RNAs. Studies in different model organisms and cell-based systems show that perturbations of Maf1 can also impact cell physiology and metabolism. These effects are mediated by changes in Pol III transcription and/or by effects of Maf1 on the expression of select Pol II-transcribed genes. Maf1 phenotypes can vary between different systems and are sometimes conflicting as in comparisons between Maf1 KO mice and cultured mammalian cells. These studies are reviewed in an effort to better appreciate the relationship between Maf1 function and cell physiology. This article is part of a Special Issue entitled: SI: Regulation of tRNA synthesis and modification in physiological conditions and disease edited by Dr. Boguta Magdalena.
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Canadian Journal of Zoology,
1988]
Nematodes have a number of biological attributes that make them amenable for molecular studies. In our laboratory, attention has focused on (i) determining the polypeptide composition of cuticles, (ii) using monoclonal antibodies to identify epitopes among the cuticular proteins, (iii) visualizing the sites of collagenous components within the cuticle of Ascaris by immunolocalization, and (iv) sequencing a moderately repetitive DNA element that is found, with extensive similarity, in the genomes of Ascaris and Panagrellus. The role of these and other molecular studies in understanding the biology of nematodes is discussed.
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Curr Opin Chem Biol,
2001]
In many species, double-stranded RNA can specifically and effectively silence genes. This newly discovered biological phenomenon, called RNA interference (RNAi), has practical implications for functional genomics. As shown by two recent reports, RNAi provides a rapid method to test the function of genes in the nematode Caenorhabditis elegans; most of the genes on C. elegans chromosome I and III have now been tested for RNAi phenotypes. The results validate RNAi as a powerful functional genomics tool for C. elegans, and point the way for similar large-scale studies in other species.
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Semin Cell Dev Biol,
2015]
R3 receptor tyrosine phosphatases (RPTPs) are characterized by extracellular domains composed solely of long chains of fibronectin type III repeats, and by the presence of a single phosphatase domain. There are five proteins in mammals with this structure, two in Drosophila and one in Caenorhabditis elegans. R3 RPTPs are selective regulators of receptor tyrosine kinase (RTK) signaling, and a number of different RTKs have been shown to be direct targets for their phosphatase activities. Genetic studies in both invertebrate model systems and in mammals have shown that R3 RPTPs are essential for tubular organ development. They also have important functions during nervous system development. R3 RPTPs are likely to be tumor suppressors in a number of types of cancer.
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Mutat Res,
2010]
Apurinic/apyrimidinic (AP) endonucleases are versatile DNA repair enzymes that possess a variety of nucleolytic activities, including endonuclease activity at AP sites, 3' phosphodiesterase activity that can remove a variety of ligation-blocking lesions from the 3' end of DNA, endonuclease activity on oxidative DNA lesions, and 3' to 5' exonuclease activity. There are two families of AP endonucleases, named for the bacterial counterparts endonuclease IV (EndoIV) and exonuclease III (ExoIII). While ExoIII family members are present in all kingdoms of life, EndoIV members exist in lower organisms but are curiously absent in plants, mammals and some other vertebrates. Here, we review recent research on these enzymes, focusing primarily on the EndoIV family. We address the role(s) of EndoIV members in DNA repair and discuss recent findings from each model organism in which the enzymes have been studied to date.
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Genes Dev,
2001]
In the few years since the discovery of RNA interference, it has become clear that this process is ancient. RNAi, the oldest and most ubiquitous antiviral system, appeared before the divergence of plants and animals. Because aspects of RNAi, known as cosuppression, also control the expression of transposable elements and repetitive sequences, the interplay of RNAi and transposon activities have almost certainly shaped the structure of the genome of most organisms. Surprisingly, we are only now beginning to explore the molecular processes responsible for RNAi and to appreciate the breadth of its function in biology. Practical applications of this knowledge have allowed rapid surveys of gene functions (see Fraser et al. 2000 and Gonczey et al. 2000 for RNAi analysis of genes on chromosome I and III of Caenorhabditis elegans) and will possibly result in new therapeutic interventions.