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https://www.readbyqxmd.com/read/29352613/mrna-translation-gone-awry-translation-fidelity-and-neurological-disease
#1
REVIEW
Mridu Kapur, Susan L Ackerman
Errors during mRNA translation can lead to a reduction in the levels of functional proteins and an increase in deleterious molecules. Advances in next-generation sequencing have led to the discovery of rare genetic disorders, many caused by mutations in genes encoding the mRNA translation machinery, as well as to a better understanding of translational dynamics through ribosome profiling. We discuss here multiple neurological disorders that are linked to errors in tRNA aminoacylation and ribosome decoding. We draw on studies from genetic models, including yeast and mice, to enhance our understanding of the translational defects observed in these diseases...
January 15, 2018: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/29352288/phospholipid-scramblase-1-interacts-with-influenza-a-virus-np-impairing-its-nuclear-import-and-thereby-suppressing-virus-replication
#2
Weiyu Luo, Jie Zhang, Libin Liang, Guangwen Wang, Qibing Li, Pengyang Zhu, Yuan Zhou, Junping Li, Yuhui Zhao, Nan Sun, Shanyu Huang, Chenchen Zhou, Yu Chang, Pengfei Cui, Pucheng Chen, Yongping Jiang, Guohua Deng, Zhigao Bu, Chengjun Li, Li Jiang, Hualan Chen
Transcription and replication of the influenza A virus (IAV) genome occur in the nucleus of infected cells and are carried out by the viral ribonucleoprotein complex (vRNP). As a major component of the vRNP complex, the viral nucleoprotein (NP) mediates the nuclear import of the vRNP complex via its nuclear localization signals (NLSs). Clearly, an effective way for the host to antagonize IAV infection would be by targeting vRNP nuclear import. Here, we identified phospholipid scramblase 1 (PLSCR1) as a binding partner of NP by using a yeast two-hybrid (Y2H) screen...
January 19, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29352245/av2-protein-of-tomato-leaf-curl-palampur-virus-promotes-systemic-necrosis-in-nicotiana-benthamiana-and-interacts-with-host-catalase2
#3
Poonam Roshan, Aditya Kulshreshtha, Surender Kumar, Rituraj Purohit, Vipin Hallan
Tomato leaf curl Palampur virus (ToLCPalV) is a whitefly-transmitted, bipartite begomovirus. Here, we demonstrated that ectopic expression of AV2 from a Potato virus X (PVX)-based vector accelerated systemic necrosis and reactive oxygen species (ROS) accumulation in Nicotiana benthamiana. Furthermore, 10 amino acids from N-terminal region of AV2 were found to be associated with the systemic necrosis symptom/phenotype. Mutational studies of ToLCPalV infectious clones lacking the AV2 revealed that AV2 is essential for the systemic movement of DNA-A, symptom severity and viral DNA accumulation...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352213/cucumber-mosaic-virus-coat-protein-induces-the-development-of-chlorotic-symptoms-through-interacting-with-the-chloroplast-ferredoxin-i-protein
#4
Yanhong Qiu, Yongjiang Zhang, Chaonan Wang, Rong Lei, Yupin Wu, Xinshi Li, Shuifang Zhu
Cucumber mosaic virus (CMV) infection could induce mosaic symptoms on a wide-range of host plants. However, there is still limited information regarding the molecular mechanism underlying the development of the symptoms. In this study, the coat protein (CP) was confirmed as the symptom determinant by exchanging the CP between a chlorosis inducing CMV-M strain and a green-mosaic inducing CMV-Q strain. A yeast two-hybrid analysis and bimolecular fluorescence complementation revealed that the chloroplast ferredoxin I (Fd I) protein interacted with the CP of CMV-M both in vitro and in vivo, but not with the CP of CMV-Q...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352143/ribosomal-protein-us7-rps5-serine-223-in-protein-kinase-mediated-phosphorylation-and-ribosomal-small-subunit-maturation
#5
Makoto Tomioka, Mitsugu Shimobayashi, Makoto Kitabatake, Mutsuhito Ohno, Yasunori Kozutsumi, Shogo Oka, Hiromu Takematsu
Cellular translation should be precisely controlled in response to extracellular cues. However, knowledge is limited concerning signal transduction-regulated translation. In the present study, phosphorylation was identified in the 40S small subunit ribosomal protein uS7 (Yjr123w/previously called as Rps5) by Ypk1 and Pkc1, AGC family protein kinases in yeast Saccharomyces cerevisiae. Serine residue 223 (Ser223) of uS7 in the conserved C-terminal region was crucial for this phosphorylation event. S223A mutant uS7 caused severe reduction of small ribosomal subunit production, likely due to compromised interaction with Rio2, resulting in both reduced translation and reduced cellular proliferation...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352080/functional-analysis-of-cancer-associated-dna-polymerase-%C3%AE%C2%B5-variants-in-saccharomyces-cerevisiae
#6
Stephanie R Barbari, Daniel P Kane, Elizabeth A Moore, Polina V Shcherbakova
DNA replication fidelity relies on base selectivity of the replicative DNA polymerases, exonucleolytic proofreading, and post-replicative DNA mismatch repair (MMR). Ultramutated human cancers without MMR defects carry alterations in the exonuclease domain of DNA polymerase ε (Polε). They have been hypothesized to result from defective proofreading. However, modeling in yeast of the most common variant, Polε-P286R, produced an unexpectedly strong mutator effect that exceeded the effect of proofreading deficiency by two orders of magnitude and indicated the involvement of other infidelity factors...
January 19, 2018: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29352017/keeping-it-real-mrx-sae2-clipping-of-natural-substrates
#7
REVIEW
Robert Gnügge, Lorraine S Symington
The yeast Mre11-Rad50-Xrs2 (MRX) complex and Sae2 function together to initiate DNA end resection, an essential early step in homology-dependent repair of DNA double-strand breaks (DSBs). In this issue of Genes & Development, Wang and colleagues (pp. 2331-2336) and Reginato and colleagues (pp. 2325-2330) report that a variety of physiological protein blocks, including Ku, RPA, and nucleosomes, stimulate MRX-Sae2 endonuclease cleavage in vitro. These studies have important implications for how cells deal with a range of barriers to end resection and highlight the crucial role of Sae2 in activating MRX cleavage at the correct cell cycle stage...
December 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/29351914/high-resolution-transcription-maps-reveal-the-widespread-impact-of-roadblock-termination-in-yeast
#8
Tito Candelli, Drice Challal, Jean-Baptiste Briand, Jocelyne Boulay, Odil Porrua, Jessie Colin, Domenico Libri
Transcription termination delimits transcription units but also plays important roles in limiting pervasive transcription. We have previously shown that transcription termination occurs when elongating RNA polymerase II (RNAPII) collides with the DNA-bound general transcription factor Reb1. We demonstrate here that many different DNA-binding proteins can induce termination by a similar roadblock (RB) mechanism. We generated high-resolution transcription maps by the direct detection of RNAPII upon nuclear depletion of two essential RB factors or when the canonical termination pathways for coding and non-coding RNAs are defective...
January 19, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29351891/overexpression-of-a-wheat-triticum-aestivum-l-bzip-transcription-factor-gene-tabzip6-decreased-the-freezing-tolerance-of-transgenic-arabidopsis-seedlings-by-down-regulating-the-expression-of-cbfs
#9
Wangting Cai, Yaling Yang, Weiwei Wang, Guangyan Guo, Wei Liu, Caili Bi
The basic leucine zipper (bZIP) proteins play important roles against abiotic stress in plants, including cold stress. However, most bZIPs involved in plant freezing tolerance are positive regulators. Only a few bZIPs function negatively in cold stress response. In this study, TabZIP6, a Group C bZIP transcription factor gene from common wheat (Triticum aestivum L.), was cloned and characterized. The transcript of TabZIP6 was strongly induced by cold treatment (4 °C). TabZIP6 is a nuclear-localized protein with transcriptional activation activity...
January 11, 2018: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/29351850/systematic-gene-to-phenotype-arrays-a-high-throughput-technique-for-molecular-phenotyping
#10
Philipp A Jaeger, Lilia Ornelas, Cameron McElfresh, Lily R Wong, Randolph Y Hampton, Trey Ideker
We have developed a highly parallel strategy, systematic gene-to-phenotype arrays (SGPAs), to comprehensively map the genetic landscape driving molecular phenotypes of interest. By this approach, a complete yeast genetic mutant array is crossed with fluorescent reporters and imaged on membranes at high density and contrast. Importantly, SGPA enables quantification of phenotypes that are not readily detectable in ordinary genetic analysis of cell fitness. We benchmark SGPA by examining two fundamental biological phenotypes: first, we explore glucose repression, in which SGPA identifies a requirement for the Mediator complex and a role for the CDK8/kinase module in regulating transcription...
January 18, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29351849/the-dfm1-derlin-is-required-for-erad-retrotranslocation-of-integral-membrane-proteins
#11
Sonya Neal, Philipp A Jaeger, Sascha H Duttke, Christopher K Benner, Christopher Glass, Trey Ideker, Randolph Hampton
Endoplasmic reticulum (ER)-associated degradation (ERAD) removes misfolded proteins from the ER membrane and lumen by the ubiquitin-proteasome pathway. Retrotranslocation of ubiquitinated substrates to the cytosol is a universal feature of ERAD that requires the Cdc48 AAA-ATPase. Despite intense efforts, the mechanism of ER exit, particularly for integral membrane (ERAD-M) substrates, has remained unclear. Using a self-ubiquitinating substrate (SUS), which undergoes normal retrotranslocation independently of known ERAD factors, and the new SPOCK (single plate orf compendium kit) micro-library to query all yeast genes, we found the rhomboid derlin Dfm1 was required for retrotranslocation of both HRD and DOA ERAD pathway integral membrane substrates...
January 18, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29351732/nutrient-depletion-and-tor-inhibition-induce-18s-and-25s-ribosomal-rnas-resistant-to-a-5-phosphate-dependent-exonuclease-in-candida-albicans-and-other-yeasts
#12
Jacob Fleischmann, Miguel A Rocha
BACKGROUND: Messenger RNA (mRNA) represents a small percentage of RNAs in a cell, with ribosomal RNA (rRNA) making up the bulk of it. To isolate mRNA from eukaryotes, typically poly-A selection is carried out. Recently, a 5´-phosphate-dependent, 5´→3´ processive exonuclease called Terminator has become available. It will digest only RNA that has a 5´-monophosphate end and therefore it is very useful to eliminate most of rRNAs in cell. RESULTS: We have found that in the pathogenic yeast Candida albicans, while 18S and 25S components isolated from yeast in robust growth phase are easily eliminated by Terminator, those isolated from cells in the nutritionally diminished stationary phase, become resistant to digestion by this enzyme...
January 19, 2018: BMC Molecular Biology
https://www.readbyqxmd.com/read/29351565/sumo-targeting-of-a-stress-tolerant-ulp1-sumo-protease
#13
Jennifer Peek, Catherine Harvey, Dreux Gray, Danny Rosenberg, Likhitha Kolla, Reuben Levy-Myers, Rui Yin, Jonathan L McMurry, Oliver Kerscher
SUMO proteases of the SENP/Ulp family are master regulators of both sumoylation and desumoylation and regulate SUMO homeostasis in eukaryotic cells. SUMO conjugates rapidly increase in response to cellular stress, including nutrient starvation, hypoxia, osmotic stress, DNA damage, heat shock, and other proteotoxic stressors. Nevertheless, little is known about the regulation and targeting of SUMO proteases during stress. To this end we have undertaken a detailed comparison of the SUMO-binding activity of the budding yeast protein Ulp1 (ScUlp1) and its ortholog in the thermotolerant yeast Kluyveromyces marxianus, KmUlp1...
2018: PloS One
https://www.readbyqxmd.com/read/29351555/omega-3-fatty-acid-desaturase-gene-family-from-two-%C3%AF-3-sources-salvia-hispanica-and-perilla-frutescens-cloning-characterization-and-expression
#14
Yufei Xue, Baojun Chen, Aung Naing Win, Chun Fu, Jianping Lian, Xue Liu, Rui Wang, Xingcui Zhang, Yourong Chai
Omega-3 fatty acid desaturase (ω-3 FAD, D15D) is a key enzyme for α-linolenic acid (ALA) biosynthesis. Both chia (Salvia hispanica) and perilla (Perilla frutescens) contain high levels of ALA in seeds. In this study, the ω-3 FAD gene family was systematically and comparatively cloned from chia and perilla. Perilla FAD3, FAD7, FAD8 and chia FAD7 are encoded by single-copy (but heterozygous) genes, while chia FAD3 is encoded by 2 distinct genes. Only 1 chia FAD8 sequence was isolated. In these genes, there are 1 to 6 transcription start sites, 1 to 8 poly(A) tailing sites, and 7 introns...
2018: PloS One
https://www.readbyqxmd.com/read/29351285/wine-yeast-phenomics-a-standardized-fermentation-method-for-assessing-quantitative-traits-of-saccharomyces-cerevisiae-strains-in-enological-conditions
#15
Emilien Peltier, Margaux Bernard, Marine Trujillo, Duyên Prodhomme, Jean-Christophe Barbe, Yves Gibon, Philippe Marullo
This work describes the set up of a small scale fermentation methodology for measuring quantitative traits of hundreds of samples in an enological context. By using standardized screw cap vessels, the alcoholic fermentation kinetics of Saccharomyces cerevisiae strains were measured by following their weight loss over the time. This dispositive was coupled with robotized enzymatic assays for measuring metabolites of enological interest in natural grape juices. Despite the small volume used, kinetic parameters and fermentation end products measured are similar with those observed in larger scale vats...
2018: PloS One
https://www.readbyqxmd.com/read/29351065/measurement-of-binding-strength-between-prey-proteins-interacting-with-toxoplasma-gondii-sag1-and-sag2-using-isothermal-titration-calorimetry-itc
#16
Meng-Yee Lai, Yee-Ling Lau
Following the outcome from a previously performed yeast two-hybrid experiment, the binding strength between T. gondii SAG1 and SAG2 and their respective prey proteins were further confirmed in this study. The sag1, sag2 and their prey genes were amplified and cloned into a pGEMT vector. To express the recombinant proteins, the fragments were then subcloned into a pRSETA vector and transformed into E. coli BL21 (DE3) cells. The recombinant proteins were expressed optimally at 37°C and 1mM of IPTG. The 6X His-tag fusion proteins were purified, dialyzed and concentrated...
March 26, 2018: Acta Parasitologica
https://www.readbyqxmd.com/read/29350807/mait-cells-and-viruses
#17
James E Ussher, Christian B Willberg, Paul Klenerman
Mucosal associated invariant T cells (MAIT cells) bear a T cell receptor (TCR) that specifically targets microbially-derived metabolites. Functionally they respond to bacteria and yeasts, which possess the riboflavin pathway, essential for production of such metabolites and which are presented on MR1. Viruses cannot generate these ligands, so a priori, they should not be recognized by MAIT cells and indeed this is true when considering recognition through the TCR. However, MAIT cells are distinctive in another respect, since they respond quite sensitively to non-TCR signals, especially in the form of inflammatory cytokines...
January 19, 2018: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29350802/cellular-reprogramming-a-new-way-to-understand-aging-mechanisms
#18
REVIEW
Burcu Yener Ilce, Umut Cagin, Acelya Yilmazer
Increased life expectancy, due to the rise in life quality and the decline in mortality rates, is leading to a society in which the population aged 60 and over is growing more rapidly than the entire population. Although various models and model organisms have been employed to investigate the mechanism of aging, induced pluripotent stem cells (iPSCs) are useful candidates to study human aging and age-related human diseases. This work discusses how iPSCs can be used as an alternative to the model organisms such as yeast, Caenorhabditis elegans, Drosophila melanogaster, or the mouse...
January 19, 2018: Wiley Interdisciplinary Reviews. Developmental Biology
https://www.readbyqxmd.com/read/29350755/microbial-and-chemical-shelf-life-of-vacuum-steam-pasteurized-whole-flaxseed-and-milled-flaxseed
#19
Manoj Shah, Bridget Eklund, Luiz Gustavo Conde Lima, Teresa Bergholz, Clifford Hall
Flaxseed is an oilseed with many health benefits. Flaxseed may be consumed raw or in processed form. In the raw form, there is a potential for microbial contamination. Several pasteurization methods have been used to reduce microbial contamination. However, such treatments may affect chemical properties of foods. In this study, vacuum steam-pasteurization was conducted on whole flaxseed and milled flaxseed using 4 different conditions (3 min at 75 °C, 3 min at 90 °C, 9 min at 90 °C, and 3 min at 105 °C)...
January 19, 2018: Journal of Food Science
https://www.readbyqxmd.com/read/29350750/the-hepatoprotective-effect-of-selenium-enriched-yeast-and-gum-arabic-combination-on-carbon-tetrachloride-induced-chronic-liver-injury-in-rats
#20
Mohammed Hamid, Yassin Abdulrahim, Dandan Liu, Gang Qian, Alamzeb Khan, Kehe Huang
The antioxidant and anti-inflammatory effects of selenium-enriched yeast (SY) and Gum Arabic (GA) have been reported. This study aimed to determine the hepatoprotective effect of SY and GA combination on carbon tetrachloride (CCl4 )-induced chronic liver injury in rats and to explore their synergistic mechanisms of action. Forty adult male Wistar rats randomly allotted to 5 groups: (A) worked as control, (B) was administered CCl4 , (C-E) were fed daily by GA, SY, and GA+SY respectively after mixing with basal diet, following CCl4 -intoxication...
January 19, 2018: Journal of Food Science
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