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[
IUBMB Life,
2000]
In the past decade, important advances have been made in our knowledge of the composition of human RNase MRP and RNase P complexes. Both ribonucleoprotein particles function as endonucleases and contain RNA components that are structurally related. RNase MRP has been suggested to be involved in the processing of precursor rRNA; RNase P, in the maturation of tRNA. Here we give an overview of current data on the structure and function of human RNase MRP and RNase P particles, with emphasis on their molecular composition. At present, seven protein subunits, probably all associated with both ribonucleoprotein particles, have been isolated and their corresponding cDNAs cloned. Although no known structural motifs can be identified in the amino acid sequences of these proteins, the majority is clearly rich in basic residues. For two protein subunits, a cluster of basic amino acids have been shown to be involved in nucleolar accumulation, whereas another protein, which lacks such a region, probably enters the nucleolus by way of a piggyback mechanism. The binding regions for several of the protein subunits on the RNA have been identified, and the data have been used to create a putative structural model for the RNase MRP particle. The rather obscure situation concerning the association of the autoantigenic Th-40 protein and its possible relationship with one of the subunits, Rpp38, is discussed.
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[
Dev Cell,
2004]
Currently, perhaps the most significant biological problem is to understand the mechanisms of learning and memory, and many of the answers will come from molecular explanations of synaptic plasticity. Two new papers have established a surprising connection: the Anaphase Promoting Complex/Cyclosome (APC/C) has a second function in controlling local protein stability at synapses, and hence in the control of behavior (Juo and Kaplan, 2004; van Roessel et al., 2004).
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[
Crit Rev Biochem Mol Biol,
2012]
The CCAAT box promoter element and NF-Y, the transcription factor (TF) that binds to it, were among the first cis-elements and trans-acting factors identified; their interplay is required for transcriptional activation of a sizeable number of eukaryotic genes. NF-Y consists of three evolutionarily conserved subunits: a dimer of NF-YB and NF-YC which closely resembles a histone, and the "innovative" NF-YA. In this review, we will provide an update on the functional and biological features that make NF-Y a fundamental link between chromatin and transcription. The last 25 years have witnessed a spectacular increase in our knowledge of how genes are regulated: from the identification of cis-acting sequences in promoters and enhancers, and the biochemical characterization of the corresponding TFs, to the merging of chromatin studies with the investigation of enzymatic machines that regulate epigenetic states. Originally identified and studied in yeast and mammals, NF-Y - also termed CBF and CP1 - is composed of three subunits, NF-YA, NF-YB and NF-YC. The complex recognizes the CCAAT pentanucleotide and specific flanking nucleotides with high specificity (Dorn et al., 1997; Hatamochi et al., 1988; Hooft van Huijsduijnen et al, 1987; Kim & Sheffery, 1990). A compelling set of bioinformatics studies clarified that the NF-Y preferred binding site is one of the most frequent promoter elements (Suzuki et al., 2001, 2004; Elkon et al., 2003; Marino-Ramirez et al., 2004; FitzGerald et al., 2004; Linhart et al., 2005; Zhu et al., 2005; Lee et al., 2007; Abnizova et al., 2007; Grskovic et al., 2007; Halperin et al., 2009; Hakkinen et al., 2011). The same consensus, as determined by mutagenesis and SELEX studies (Bi et al., 1997), was also retrieved in ChIP-on-chip analysis (Testa et al., 2005; Ceribelli et al., 2006; Ceribelli et al., 2008; Reed et al., 2008). Additional structural features of the CCAAT box - position, orientation, presence of multiple Transcriptional Start Sites - were previously reviewed (Dolfini et al., 2009) and will not be considered in detail here.
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[
1983]
In 1974, Sydney Brenner published an elegant paper that described the genetic system of Caenorhabditis elegans and led to its use in research on a wide variety of topics, including aging (Brenner, 1974). Its small size (1mm as an adult) and determinate cell lineage has allowed a description of the entire somatic cell lineage from the one-cell stage to the adult (Sulston and Horvitz, 1977; Deppe et al., 1978; Kimble and Hirsh, 1979; Suslton et al., personal communication). Its ease of culture makes it an organism of choice for studies of various aspects of anatomy and physiology, including muscle formation and function (Zengel and Epstein, 1980; Mackenzie and Epstein, 1980), cuticle formation (Cox et al, 1981), neuroanatomy (Ward et al, 1975; Ware et al, 1975; Sulston et al, 1975), and behavior (Dusenbery, 1980). Several genes have been cloned by recombinant DNA techniques ablation (Kimble, 1981; Laufer and von Ehrenstin, 1981) procedures, as well as most of the modern molecular techniques, are in use.
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[
Cell,
1997]
The demonstrations in two papers in this issue of Cell (Rocheleau et al., 1997; Thorpe et al., 1997) of the involvement of a Wnt pathway in very early embryogenesis in Caenorhabditis elegans provides another significant step toward the ambitious but realistic goal of understanding all the basic strategies used to control embryogenesis in this model organism. At the same time, they challenge some of the prevailing models of Wnt signaling, suggesting that interactions among Wnt pathway components may vary in different developmental processes. With these papers, as well as the earlier reports on Wnt pathway genes
lin-44,
lin-17, and
pop-1 (Herman et al., 1995; Lin et al., 1995; Harris et al., 1996; Sawa et al., 1996) and new studies on Wnt pahtway genes reported in recent meetings, worm breeders have become a significant force in the army of Wnt researchers. They have also illustrated how different systems can provide important new complementary insights.
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[
Front Cell Dev Biol,
2020]
Stem cell development depends on post-transcriptional regulation mediated by RNA-binding proteins (RBPs) (Zhang et al., 1997; Forbes and Lehmann, 1998; Okano et al., 2005; Ratti et al., 2006; Kwon et al., 2013). Pumilio and FBF (PUF) family RBPs are highly conserved post-transcriptional regulators that are critical for stem cell maintenance (Wickens et al., 2002; Quenault et al., 2011). The RNA-binding domains of PUF proteins recognize a family of related sequence motifs in the target mRNAs, yet individual PUF proteins have clearly distinct biological functions (Lu et al., 2009; Wang et al., 2018). The <i>C. elegans</i> germline is a simple and powerful model system for analyzing regulation of stem cell development. Studies in <i>C. elegans</i> uncovered specific physiological roles for PUFs expressed in the germline stem cells ranging from control of proliferation and differentiation to regulation of the sperm/oocyte decision. Importantly, recent studies started to illuminate the mechanisms behind PUF functional divergence. This review summarizes the many roles of PUF-8, FBF-1, and FBF-2 in germline stem and progenitor cells (SPCs) and discusses the factors accounting for their distinct biological functions. PUF proteins are conserved in evolution, and insights into PUF-mediated regulation provided by the <i>C. elegans</i> model system are likely relevant for other organisms.
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[
Cell,
2004]
Heterotrimeric G proteins are well known for their function in signal transduction downstream of seven transmembrane receptors. More recently, however, genetic analysis in C. elegans and in Drosophila has revealed a second, essential function of these molecules in positioning the mitotic spindle and attaching microtubules to the cell cortex. Five new publications in Cell (Afshar et al., 2004; Du and Macara, 2004 [this issue of Cell]; Hess et al., 2004), Developmental Cell (Martin-McCaffrey et al., 2004), and Current Biology (Couwenbergs et al., 2004) show that this function is conserved in vertebrates and-like the classical pathway- involves cycling of G proteins between GDP and GTP bound conformations.
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[
Methods Cell Biol,
2012]
This chapter is dedicated to the study of aging in Caenorhabditis elegans (C. elegans). The assays are divided into two sections. In the first section, we describe detailed protocols for performing life span analysis in solid and liquid medium. In the second section, we describe various assays for measuring age-related changes. Our laboratory has been involved in several fruitful collaborations with non-C. elegans researchers keen on testing a role for their favorite gene in modulating aging (Carrano et al., 2009; Dong et al., 2007; Raices et al., 2008; Wolff et al., 2006). But even with the guidance of trained worm biologists, this undertaking can be daunting. We hope that this chapter will serve as a worthy compendium for those researchers who may or may not have immediate access to laboratories studying C. elegans.
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[
1982]
The small soil nematode Caenorhabditis elegans is an attractive organism for the molecular study of muscle function and development because of its anatomical simplicity and suitability for genetic and biochemical analysis (Brenner 1974; Sulston and Horvitz 1977). The body-wall musculature of C. elegans is composed of 95 cell disposed in four quadrants, which run the length of the animal beneath the cuticle. The musculature is obliquely striated, and the sarcomeres are oriented parallel to the long axis of the animal. Since these cells represent a large reaction of the animal mass, isolation of contractile proteins is comparatively simple (Epstein et al. 1974; Waterston et al. 1974, 1977a; Harris and Epstein 1977; Mackenzie and Epstein 1980). Mutants affecting the characteristic pattern of motility of C. elegans can be easily identified, and microscopic examination of these "uncoordinated," or unc strains, in the living animal by polarized light microscopy or, more carefully, by electron microscopy has led to the identification of 22 genes that produce altered muscle phenotypes (Waterston et al. 1980; Zengel and Epstein 1980). Of these, two are known to code for major structural proteins of muscle: The
unc-54 gene codes for the major heavy chain of myosin (Epstein et al. 1974; MacLeod et al. 1977b), whereas the un-15 gene codes for paramyosin, the core protein of the thick filaments (Waterston et al. 1974; MacLeod et al. 1977a; Harris and Epstein 1977).
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[
Adv Exp Med Biol,
1988]
Parasite-specific putrescine-N-acetyltransferase and polyamine oxidase, both involved in the reversed pathway of polyamine metabolism, were demonstrated for Ascaris suum and Onchocerca volvulus. Berenil-treatment was found to be correlated with accumulation of polyamines, especially spermine, obviously due to blockaded polyamine interconversion. Furthermore it was shown that added spermine to the culture medium led to the death of worms. These specificities might be exploited for chemotherapy of filarial infections. Polyamines are widely distributed in the nature. They are found in higher and lower eucaryotes and in procaryotes as well as in viruses (Tabor and Tabor, 1984). During the last years there have been many approaches to examine the role of polyamines in cell growth and differentiation in vertebrates (Tabor and Tabor, 1984; Pegg, 1986). The polyamine metabolism of parasites also has attracted increasing interest, e.g. in African trypanosomes the initial enzyme of polyamine synthesis - ornithine decarboxylase - has been exploited as a target for chemotherapy by using DFMO (DL alpha-difluoromethylornithine) (Bacchi et al., 1980; Bacchi et al., 1983; Fairlamb et al., 1985; Giffin et al., 1986). The polyamine metabolism of filaria and other helminths is still a neglected area of research, although there are reports about distribution pattern of polyamines and some peculiarities of polyamine metabolism in filarial worms (Srivastava et al., 1980; Wittich et al., 1987; Walter, 1988). DFMO and MGBG (methylglyoxal bis-(guanylhydrazone], both of which are potent inhibitors of polyamine synthesis in mammals, do not significantly effect the viability of filarial worms (Wittich et al., 1987).(ABSTRACT TRUNCATED AT 250 WORDS)