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https://www.readbyqxmd.com/read/28334955/the-schizosaccharomyces-pombe-ppr-protein-ppr10-associates-with-a-novel-protein-mpa1-and-acts-as-a-mitochondrial-translational-activator
#1
Yirong Wang, Jianhua Yan, Qingzhen Zhang, Xuting Ma, Juan Zhang, Minghui Su, Xiaojun Wang, Ying Huang
The pentatricopeptide repeat (PPR) proteins characterized by tandem repeats of a degenerate 35-amino-acid motif function in all aspects of organellar RNA metabolism, many of which are essential for organellar gene expression. In this study, we report the characterization of a fission yeast Schizosaccharomyces pombe PPR protein, Ppr10 and a novel Ppr10-associated protein, designated Mpa1. The ppr10 deletion mutant exhibits growth defects in respiratory media, and is dramatically impaired for viability during the late-stationary phase...
February 22, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334913/tdp-43-mutations-causing-amyotrophic-lateral-sclerosis-are-associated-with-altered-expression-of-rna-binding-protein-hnrnp-k-and-affect-the-nrf2-antioxidant-pathway
#2
Diane Moujalled, Alexandra Grubman, Karla Acevedo, Shu Yang, Yazi D Ke, Donia M Moujalled, Clare Duncan, Aphrodite Caragounis, Nirma D Perera, Bradley J Turner, Mercedes Prudencio, Leonard Petrucelli, Ian Blair, Lars M Ittner, Peter J Crouch, Jeffrey R Liddell, Anthony R White
TAR DNA binding protein 43 (TDP-43) is a major disease-associated protein involved in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U). Our previous studies found a direct association between TDP-43 and heterogeneous nuclear ribonucleoprotein K (hnRNP K). In this study, utilizing ALS patient fibroblasts harboring a TDP-43M337V mutation and NSC-34 motor neuronal cell line expressing TDP-43Q331K mutation, we show that hnRNP K expression is impaired in urea soluble extracts from mutant TDP-43 cell models...
March 9, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334903/n6-methyladenosine-alters-rna-structure-to-regulate-binding-of-a-low-complexity-protein
#3
Nian Liu, Katherine I Zhou, Marc Parisien, Qing Dai, Luda Diatchenko, Tao Pan
N6-methyladenosine (m6A) is the most abundant internal modification in eukaryotic messenger RNA (mRNA), and affects almost every stage of the mRNA life cycle. The YTH-domain proteins can specifically recognize m6A modification to control mRNA maturation, translation and decay. m6A can also alter RNA structures to affect RNA-protein interactions in cells. Here, we show that m6A increases the accessibility of its surrounding RNA sequence to bind heterogeneous nuclear ribonucleoprotein G (HNRNPG). Furthermore, HNRNPG binds m6A-methylated RNAs through its C-terminal low-complexity region, which self-assembles into large particles in vitro...
February 25, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334834/aav-mediated-transfer-of-fkrp-shows-therapeutic-efficacy-in-a-murine-model-but-requires-control-of-gene-expression
#4
Evelyne Gicquel, Natacha Maizonnier, Steven J Foltz, William J Martin, Nathalie Bourg, Fedor Svinartchouk, Karine Charton, Aaron M Beedle, Isabelle Richard
Limb Girdle Muscular Dystrophies type 2I (LGMD2I), a recessive autosomal muscular dystrophy, is caused by mutations in the Fukutin Related Protein (FKRP) gene. It has been proposed that FKRP, a ribitol-5-phosphate transferase, is a participant in α-dystroglycan (αDG) glycosylation, which is important to ensure the cell/matrix anchor of muscle fibers. A LGMD2I knock-in mouse model was generated to express the most frequent mutation (L276I) encountered in patients. The expression of FKRP was not altered neither at transcriptional nor at translational levels, but its function was impacted since abnormal glycosylation of αDG was observed...
March 3, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334758/n1-methyl-pseudouridine-in-mrna-enhances-translation-through-eif2%C3%AE-dependent-and-independent-mechanisms-by-increasing-ribosome-density
#5
Yuri V Svitkin, Yi Min Cheng, Tirtha Chakraborty, Vladimir Presnyak, Matthias John, Nahum Sonenberg
Certain chemical modifications confer increased stability and low immunogenicity to in vitro transcribed mRNAs, thereby facilitating expression of therapeutically important proteins. Here, we demonstrate that N1-methyl-pseudouridine (N1mΨ) outperforms several other nucleoside modifications and their combinations in terms of translation capacity. Through extensive analysis of various modified transcripts in cell-free translation systems, we deconvolute the different components of the effect on protein expression independent of mRNA stability mechanisms...
February 23, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334756/measurements-of-translation-initiation-from-all-64-codons-in-e-coli
#6
Ariel Hecht, Jeff Glasgow, Paul R Jaschke, Lukmaan A Bawazer, Matthew S Munson, Jennifer R Cochran, Drew Endy, Marc Salit
Our understanding of translation underpins our capacity to engineer living systems. The canonical start codon (AUG) and a few near-cognates (GUG, UUG) are considered as the 'start codons' for translation initiation in Escherichia coli. Translation is typically not thought to initiate from the 61 remaining codons. Here, we quantified translation initiation of green fluorescent protein and nanoluciferase in E. coli from all 64 triplet codons and across a range of DNA copy number. We detected initiation of protein synthesis above measurement background for 47 codons...
February 21, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334742/recognition-but-no-repair-of-abasic-site-in-single-stranded-dna-by-human-ribosomal-us3-protein-residing-within-intact-40s-subunit
#7
Anastasia S Grosheva, Dmitry O Zharkov, Joachim Stahl, Alexander V Gopanenko, Alexey E Tupikin, Marsel R Kabilov, Dmitri M Graifer, Galina G Karpova
Isolated human ribosomal protein uS3 has extra-ribosomal functions including those related to base excision DNA repair, e.g. AP lyase activity that nicks double-stranded (ds) DNA 3΄ to the abasic (AP) site. However, the ability of uS3 residing within ribosome to recognize and cleave damaged DNA has never been addressed. Here, we compare interactions of single-stranded (ss) DNA and dsDNA bearing AP site with human ribosome-bound uS3 and with the isolated protein, whose interactions with ssDNA were not yet studied...
January 30, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334682/phytochemical-induced-nucleolar-stress-results-in-the-inhibition-of-breast-cancer-cell-proliferation
#8
Anna Lewinska, Diana Bednarz, Jagoda Adamczyk-Grochala, Maciej Wnuk
The nucleolus is a stress sensor and compromised nucleolar activity may be considered as an attractive anticancer strategy. In the present study, the effects of three plant-derived natural compounds, i.e., sulforaphane (SFN), ursolic acid (UA) and betulinic acid (BA) on nucleolar state were investigated in breast cancer cell lines of different receptor status, namely MCF-7, MDA-MB-231 and SK-BR-3 cells. Cytostatic action of phytochemicals against breast cancer cells was observed at low micromolar concentration window (5-20µM) and mediated by elevated p21 levels, and cell proliferation of SFN-, UA- and BA-treated normal human mammary epithelial cells (HMEC) was unaffected...
March 14, 2017: Redox Biology
https://www.readbyqxmd.com/read/28334640/mirnas-in-synapse-development-and-synaptic-plasticity
#9
REVIEW
Zhonghua Hu, Zheng Li
Synapses are functional units of the nervous system, through which information is transferred between neurons. The development and activity-dependent modification of synapses require temporally and spatially controlled modulation of gene expression. microRNAs (miRNAs) have emerged as essential regulators of gene expression. They are small non-coding RNAs that regulate mRNA stability and translation by interacting with the 3' untranslated region (3' UTR) of mRNAs. miRNAs are located to neuronal processes to regulate protein synthesis locally and their expression is regulated by synaptic activity...
March 20, 2017: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/28334607/the-sarm1-toll-interleukin-1-receptor-domain-possesses-intrinsic-nad-cleavage-activity-that-promotes-pathological-axonal-degeneration
#10
Kow Essuman, Daniel W Summers, Yo Sasaki, Xianrong Mao, Aaron DiAntonio, Jeffrey Milbrandt
Axonal degeneration is an early and prominent feature of many neurological disorders. SARM1 is the central executioner of the axonal degeneration pathway that culminates in depletion of axonal NAD(+), yet the identity of the underlying NAD(+)-depleting enzyme(s) is unknown. Here, in a series of experiments using purified proteins from mammalian cells, bacteria, and a cell-free protein translation system, we show that the SARM1-TIR domain itself has intrinsic NADase activity-cleaving NAD(+) into ADP-ribose (ADPR), cyclic ADPR, and nicotinamide, with nicotinamide serving as a feedback inhibitor of the enzyme...
March 22, 2017: Neuron
https://www.readbyqxmd.com/read/28334491/mutant-exon1-huntingtin-aggregation-is-regulated-by-t3-phosphorylation-induced-structural-changes-and-crosstalk-between-t3-phosphorylation-and-acetylation-at-k6
#11
Anass Chiki, Sean M DeGuire, Francesco S Ruggeri, Domenico Sanfelice, Annalisa Ansaloni, Zhe-Ming Wang, Urszula Cendrowska, Ritwik Burai, Sophie Vieweg, Annalisa Pastore, Giovanni Dietler, Hilal A Lashuel
Herein, we used protein semisynthesis to investigate, for the first time, the effect of lysine acetylation and phosphorylation, as well as the crosstalk between these modifications on the structure and aggregation of mutant huntingtin exon1 (Httex1). Our results demonstrate that phosphorylation at T3 stabilizes the α-helical conformation of the N-terminal 17 amino acids (Nt17) and significantly inhibits the aggregation of mutant Httex1. Acetylation of single lysine residues, K6, K9 or K15, had no effect on Httex1 aggregation...
March 23, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28334257/fast-clash-free-rna-conformational-morphing-using-molecular-junctions
#12
Amélie Héliou, Dominik Budday, Rasmus Fonseca, Henry van den Bedem
Motivation: Non-coding ribonucleic acids (ncRNA) are functional RNA molecules that are not translated into protein. They are extremely dynamic, adopting diverse conformational substates, which enables them to modulate their interaction with a large number of other molecules. The flexibility of ncRNA provides a challenge for probing their complex 3D conformational landscape, both experimentally and computationally. Despite their conformational diversity, ncRNAs mostly preserve their secondary structure throughout the dynamic ensemble...
March 13, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28334215/systematic-inference-of-functional-phosphorylation-events-in-yeast-metabolism
#13
Yu Chen, Yonghong Wang, Jens Nielsen
Motivation: Protein phosphorylation is a post-translational modification that affects proteins by changing their structure and conformation in a rapid and reversible way, and it is an important mechanism for metabolic regulation in cells. Phosphoproteomics enables high-throughput identification of phosphorylation events on metabolic enzymes, but identifying functional phosphorylation events still requires more detailed biochemical characterization. Therefore, development of computational methods for investigating unknown functions of a large number of phosphorylation events identified by phosphoproteomics has received increased attention...
March 2, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28334050/improving-transcriptome-de-novo-assembly-by-using-a-reference-genome-of-a-related-species-translational-genomics-from-oil-palm-to-coconut
#14
Alix Armero, Luc Baudouin, Stéphanie Bocs, Dominique This
The palms are a family of tropical origin and one of the main constituents of the ecosystems of these regions around the world. The two main species of palm represent different challenges: coconut (Cocos nucifera L.) is a source of multiple goods and services in tropical communities, while oil palm (Elaeis guineensis Jacq) is the main protagonist of the oil market. In this study, we present a workflow that exploits the comparative genomics between a target species (coconut) and a reference species (oil palm) to improve the transcriptomic data, providing a proteome useful to answer functional or evolutionary questions...
2017: PloS One
https://www.readbyqxmd.com/read/28333692/application-of-olfactory-tissue-and-its-neural-progenitors-to-schizophrenia-and-psychiatric-research
#15
Joëlle Lavoie, Akira Sawa, Koko Ishizuka
PURPOSE OF REVIEW: The goal of this review article is to introduce olfactory epithelium-derived cell/tissue models as a promising surrogate system to study the molecular mechanisms implicated in schizophrenia and other neuropsychiatric disorders. Here, we particularly focus on the utility of their neural progenitors. RECENT FINDINGS: Recent investigations of the pathophysiology of schizophrenia using olfactory epithelium-derived tissue/cell models have provided insights about schizophrenia-associated alterations in neurodevelopment, stress response, and gene/protein expression regulatory pathways...
March 22, 2017: Current Opinion in Psychiatry
https://www.readbyqxmd.com/read/28333377/circadian-rhythms-in-adipose-tissue-physiology
#16
Jana-Thabea Kiehn, Anthony H Tsang, Isabel Heyde, Brinja Leinweber, Isa Kolbe, Alexei Leliavski, Anthony H Tsang
The different types of adipose tissues fulfill a wide range of biological functions-from energy storage to hormone secretion and thermogenesis-many of which show pronounced variations over the course of the day. Such 24-h rhythms in physiology and behavior are coordinated by endogenous circadian clocks found in all tissues and cells, including adipocytes. At the molecular level, these clocks are based on interlocked transcriptional-translational feedback loops comprised of a set of clock genes/proteins. Tissue-specific clock-controlled transcriptional programs translate time-of-day information into physiologically relevant signals...
March 16, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28333336/comparative-sperm-proteomics-in-mouse-species-with-divergent-mating-systems
#17
Alberto Vicens, Kirill Borziak, Timothy L Karr, Eduardo R S Roldan, Steve Dorus
Sexual selection is the pervasive force underlying the dramatic divergence of sperm form and function. Although it has been demonstrated that testis gene expression evolves rapidly, exploration of the proteomic basis of sperm diversity is in its infancy. We have employed a whole-cell proteomics approach to characterize sperm divergence among closely related Mus species that experience different sperm competition regimes and exhibit pronounced variation in sperm energetics, motility and fertilization capacity...
February 25, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28333140/metabolic-and-molecular-insights-into-an-essential-role-of-nicotinamide-phosphoribosyltransferase
#18
Li Q Zhang, Leon Van Haandel, Min Xiong, Peixin Huang, Daniel P Heruth, Charlie Bi, Roger Gaedigk, Xun Jiang, Ding-You Li, Gerald Wyckoff, Dmitry N Grigoryev, Li Gao, Linheng Li, Min Wu, J Steven Leeder, Shui Qing Ye
Nicotinamide phosphoribosyltransferase (NAMPT) is a pleiotropic protein implicated in the pathogenesis of acute respiratory distress syndrome, aging, cancer, coronary heart diseases, diabetes, nonalcoholic fatty liver disease, obesity, rheumatoid arthritis, and sepsis. However, the underlying molecular mechanisms of NAMPT in these physiological and pathological processes are not fully understood. Here, we provide experimental evidence that a Nampt gene homozygous knockout (Nampt(-/-)) resulted in lethality at an early stage of mouse embryonic development and death within 5-10 days in adult mice accompanied by a 25...
March 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28332758/microrna-microrna-complementarity-is-important-for-the-regulation-pattern-of-nfya5-by-mir169-under-dehydration-shock-in-arabidopsis
#19
Qingguo Du, Meng Zhao, Wei Gao, Suzhen Sun, Wen-Xue Li
MicroRNAs regulate gene expression at the mRNA and translational levels. Although our previous research showed that expression of miR169 and one of its targets, NFYA5, is down- and up-regulated by drought stress, respectively, the current study shows that expression of both miR169 and NFYA5 are induced by dehydration shock. Unlike overexpression of MIR169a/b, overexpression of MIR169i/l did not decrease NFYA5 transcripts but increased NFYA5 protein levels. NFYA5 protein abundance also increased in mir169a knock-out mutants and 35S::MIR169l mir169a double mutants...
March 23, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28332497/epigenetically-driven-anatomical-diversity-of-synovial-fibroblasts-guides-joint-specific-fibroblast-functions
#20
Mojca Frank-Bertoncelj, Michelle Trenkmann, Kerstin Klein, Emmanuel Karouzakis, Hubert Rehrauer, Anna Bratus, Christoph Kolling, Maria Armaka, Andrew Filer, Beat A Michel, Renate E Gay, Christopher D Buckley, George Kollias, Steffen Gay, Caroline Ospelt
A number of human diseases, such as arthritis and atherosclerosis, include characteristic pathology in specific anatomical locations. Here we show transcriptomic differences in synovial fibroblasts from different joint locations and that HOX gene signatures reflect the joint-specific origins of mouse and human synovial fibroblasts and synovial tissues. Alongside DNA methylation and histone modifications, bromodomain and extra-terminal reader proteins regulate joint-specific HOX gene expression. Anatomical transcriptional diversity translates into joint-specific synovial fibroblast phenotypes with distinct adhesive, proliferative, chemotactic and matrix-degrading characteristics and differential responsiveness to TNF, creating a unique microenvironment in each joint...
March 23, 2017: Nature Communications
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