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The tRNA methyltransferase Dnmt2 is required for accurate polypeptide synthesis during haematopoiesis 下载免费PDF全文
Francesca Tuorto Friederike Herbst Nader Alerasool Sebastian Bender Oliver Popp Giuseppina Federico Sonja Reitter Reinhard Liebers Georg Stoecklin Hermann‐Josef Gröne Gunnar Dittmar Hanno Glimm Frank Lyko 《The EMBO journal》2015,34(18):2350-2362
The Dnmt2 enzyme utilizes the catalytic mechanism of eukaryotic DNA methyltransferases to methylate several tRNAs at cytosine 38. Dnmt2 mutant mice, flies, and plants were reported to be viable and fertile, and the biological function of Dnmt2 has remained elusive. Here, we show that endochondral ossification is delayed in newborn Dnmt2‐deficient mice, which is accompanied by a reduction of the haematopoietic stem and progenitor cell population and a cell‐autonomous defect in their differentiation. RNA bisulfite sequencing revealed that Dnmt2 methylates C38 of tRNA AspGTC, GlyGCC, and ValAAC, thus preventing tRNA fragmentation. Proteomic analyses from primary bone marrow cells uncovered systematic differences in protein expression that are due to specific codon mistranslation by tRNAs lacking Dnmt2‐dependent methylation. Our observations demonstrate that Dnmt2 plays an important role in haematopoiesis and define a novel function of C38 tRNA methylation in the discrimination of near‐cognate codons, thereby ensuring accurate polypeptide synthesis. 相似文献
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The binary nucleation of phase-separated Lennard-Jones clusters was analysed under various system conditions using molecular dynamics simulations. The modified potential model provides a simple gateway to observe non-wetting behaviour and imitates the more complex interactions of non-miscible substances. Thus, not only the transition from ideally mixed clusters to so-called ‘Janus’ particles, but also the structural aspects and dynamic formation processes of nanoscopic droplets are directly observable from the gas phase. Various shapes and sizes of these inhomogeneous clusters have been found via simple tuning of system parameters. From this analysis, we gained further insight into the direct formation of ‘Janus’ particles from the gas phase. 相似文献
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Martina Höckner Reinhard Dallinger Stephen R. Stürzenbaum 《Journal of biological inorganic chemistry》2011,16(7):1057-1065
Metallobiologists have, at large, neglected soil dwelling invertebrates; exceptions are the nematode (Caenorhabditis elegans) and snails (Helix pomatia and Cantareus aspersus). This review aims to compare and contrast the molecular, protein and cellular mechanisms of the multifunctional nematode
and snail metallothioneins (MTs). The C. elegans genome contains two MT genes, mtl-1, which is constitutively expressed in the pharynx and likely to act as an essential and/or toxic metal sensor, and mtl-2, which plays a negligible role under normal physiological conditions but is strongly induced (as mtl-1) in intestinal cells upon metal exposure. It has been possible to follow the intricate phenotypic responses upon the knockdown/knockout
of single and multiple MT isoforms and we have started to decipher the multifunctional role of C. elegans MTs. The snails have contributed to our understanding regarding MT evolution and diversity, structure and metal-specific
functionality. The H. pomatia and C. aspersus genomes contain at least three MT isoform genes. CdMT is responsible for cadmium detoxification, CuMT is involved in copper
homeostasis and Cd/CuMT is a putative ancestral MT possibly only of minor importance in metal metabolism. Further investigations
of nematode, snail and other invertebrate MTs will allow the development of alternative biomarker approaches and lead to an
improved understanding of metallobiology, protein evolution and toxicogenomics. 相似文献
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B Huber A Whibley Y L Poul N Navarro A Martin S Baxter A Shah B Gilles T Wirth W O McMillan M Joron 《Heredity》2015,114(5):515-524
Understanding the genetic architecture of adaptive traits has been at the centre of modern evolutionary biology since Fisher; however, evaluating how the genetic architecture of ecologically important traits influences their diversification has been hampered by the scarcity of empirical data. Now, high-throughput genomics facilitates the detailed exploration of variation in the genome-to-phenotype map among closely related taxa. Here, we investigate the evolution of wing pattern diversity in Heliconius, a clade of neotropical butterflies that have undergone an adaptive radiation for wing-pattern mimicry and are influenced by distinct selection regimes. Using crosses between natural wing-pattern variants, we used genome-wide restriction site-associated DNA (RAD) genotyping, traditional linkage mapping and multivariate image analysis to study the evolution of the architecture of adaptive variation in two closely related species: Heliconius hecale and H. ismenius. We implemented a new morphometric procedure for the analysis of whole-wing pattern variation, which allows visualising spatial heatmaps of genotype-to-phenotype association for each quantitative trait locus separately. We used the H. melpomene reference genome to fine-map variation for each major wing-patterning region uncovered, evaluated the role of candidate genes and compared genetic architectures across the genus. Our results show that, although the loci responding to mimicry selection are highly conserved between species, their effect size and phenotypic action vary throughout the clade. Multilocus architecture is ancestral and maintained across species under directional selection, whereas the single-locus (supergene) inheritance controlling polymorphism in H. numata appears to have evolved only once. Nevertheless, the conservatism in the wing-patterning toolkit found throughout the genus does not appear to constrain phenotypic evolution towards local adaptive optima. 相似文献
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A new halacarid species, Halacarellus fontinalis n. sp., from a spring in the Gesäuse National Park, Austria is described. The species is characterized by three pairs of large, equal-sized acetabula and slender claws and is expected to have evolved in the Tertiary from a Tethyan-Paratethyan Halacarellus species. CaspihalacarusViets, 1928, with a single species, C. hyrcanusViets, 1928, has large and external acetabula similar to those in H. fontinalis. Caspihalacarus is synonymized with Halacarellus. 相似文献
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Silke Krüger Casey S. Butler Reinhard Lakes-Harlan 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》2011,197(2):181-192
Orthopterans are suitable model organisms for investigations of regeneration mechanisms in the auditory system. Regeneration
has been described in the auditory systems of locusts (Caelifera) and of crickets (Ensifera). In this study, we comparatively
investigate the neural regeneration in the auditory system in the bush cricket Mecopoda elongata. A crushing of the tympanal nerve in the foreleg of M. elongata results in a loss of auditory information transfer. Physiological recordings of the tympanal nerve suggest outgrowing fibers
5 days after crushing. An anatomical regeneration of the fibers within the central nervous system starts 10 days after crushing.
The neuronal projection reaches the target area at day 20. Threshold values to low frequency airborne sound remain high after
crushing, indicating a lower regeneration capability of this group of fibers. However, within the central target area the
low frequency areas are also innervated. Recordings of auditory interneurons show that the regenerating fibers form new functional
connections starting at day 20 after crushing. 相似文献