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https://www.readbyqxmd.com/read/28538735/ensemble-cryo-em-elucidates-the-mechanism-of-translation-fidelity
#1
Anna B Loveland, Gabriel Demo, Nikolaus Grigorieff, Andrei A Korostelev
Gene translation depends on accurate decoding of mRNA, the structural mechanism of which remains poorly understood. Ribosomes decode mRNA codons by selecting cognate aminoacyl-tRNAs delivered by elongation factor Tu (EF-Tu). Here we present high-resolution structural ensembles of ribosomes with cognate or near-cognate aminoacyl-tRNAs delivered by EF-Tu. Both cognate and near-cognate tRNA anticodons explore the aminoacyl-tRNA-binding site (A site) of an open 30S subunit, while inactive EF-Tu is separated from the 50S subunit...
May 24, 2017: Nature
https://www.readbyqxmd.com/read/28538188/identification-and-characterization-of-a-class-of-malat1-like-genomic-loci
#2
Bin Zhang, Yuntao S Mao, Sarah D Diermeier, Irina V Novikova, Eric P Nawrocki, Tom A Jones, Zsolt Lazar, Chang-Shung Tung, Weijun Luo, Sean R Eddy, Karissa Y Sanbonmatsu, David L Spector
The MALAT1 (Metastasis-Associated Lung Adenocarcinoma Transcript 1) gene encodes a noncoding RNA that is processed into a long nuclear retained transcript (MALAT1) and a small cytoplasmic tRNA-like transcript (mascRNA). Using an RNA sequence- and structure-based covariance model, we identified more than 130 genomic loci in vertebrate genomes containing the MALAT1 3' end triple-helix structure and its immediate downstream tRNA-like structure, including 44 in the green lizard Anolis carolinensis. Structural and computational analyses revealed a co-occurrence of components of the 3' end module...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28534666/human-aminoacyl-trna-synthetases-in-diseases-of-the-nervous-system
#3
Jana Ognjenović, Miljan Simonović
Aminoacyl-tRNA synthetases (AaRSs) are ubiquitously expressed enzymes that ensure accurate translation of the genetic information into functional proteins. These enzymes also execute a variety of non-canonical functions that are significant for regulation of diverse cellular processes and that reside outside the realm of protein synthesis. Associations between faults in AaRS-mediated processes and human diseases have been long recognized. Most recent research findings strongly argue that 10 cytosolic and 14 mitochondrial AaRSs are implicated in some form of pathology of the human nervous system...
May 23, 2017: RNA Biology
https://www.readbyqxmd.com/read/28533334/the-evolutionary-basis-of-translational-accuracy-in-plants
#4
Salvatore Camiolo, Gaurav Sablok, Andrea Porceddu
Mistranslation errors compromise fitness by wasting resources on nonfunctional proteins. In order to reduce the cost of mistranslations, natural selection chooses the most accurately-translated codons at sites that are particularly important for protein structure and function. We investigated the determinants underlying selection for translational accuracy in several species of plants belonging to three clades: the Brassicaceae, Fabidae and Poaceae. Although signatures of translational selection were found in genes from a wide range of species, the underlying factors varied in nature and intensity...
May 22, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28532394/circularlogo-a-lightweight-web-application-to-visualize-intra-motif-dependencies
#5
Zhenqing Ye, Tao Ma, Michael T Kalmbach, Surendra Dasari, Jean-Pierre A Kocher, Liguo Wang
BACKGROUND: The sequence logo has been widely used to represent DNA or RNA motifs for more than three decades. Despite its intelligibility and intuitiveness, the traditional sequence logo is unable to display the intra-motif dependencies and therefore is insufficient to fully characterize nucleotide motifs. Many methods have been developed to quantify the intra-motif dependencies, but fewer tools are available for visualization. RESULT: We developed CircularLogo, a web-based interactive application, which is able to not only visualize the position-specific nucleotide consensus and diversity but also display the intra-motif dependencies...
May 22, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28531330/structural-basis-for-substrate-binding-and-catalytic-mechanism-of-a-human-rna-m5c-methyltransferase-nsun6
#6
Ru-Juan Liu, Tao Long, Jing Li, Hao Li, En-Duo Wang
5-methylcytosine (m5C) modifications of RNA are ubiquitous in nature and play important roles in many biological processes such as protein translational regulation, RNA processing and stress response. Aberrant expressions of RNA:m5C methyltransferases are closely associated with various human diseases including cancers. However, no structural information for RNA-bound RNA:m5C methyltransferase was available until now, hindering elucidation of the catalytic mechanism behind RNA:m5C methylation. Here, we have solved the structures of NSun6, a human tRNA:m5C methyltransferase, in the apo form and in complex with a full-length tRNA substrate...
May 22, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28531329/alternative-stable-conformation-capable-of-protein-misinteraction-links-trna-synthetase-to-peripheral-neuropathy
#7
David Blocquel, Sheng Li, Na Wei, Herwin Daub, Mathew Sajish, Maria-Luise Erfurth, Grace Kooi, Jiadong Zhou, Ge Bai, Paul Schimmel, Albena Jordanova, Xiang-Lei Yang
While having multiple aminoacyl-tRNA synthetases implicated in Charcot-Marie-Tooth (CMT) disease suggests a common mechanism, a defect in enzymatic activity is not shared among the CMT-causing mutants. Protein misfolding is a common hypothesis underlying the development of many neurological diseases. Its process usually involves an initial reduction in protein stability and then the subsequent oligomerization and aggregation. Here, we study the structural effect of three CMT-causing mutations in tyrosyl-tRNA synthetase (TyrRS or YARS)...
May 22, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28531275/molecular-envelope-and-atomic-model-of-an-anti-terminated-glyqs-t-box-regulator-in-complex-with-trnagly
#8
Bhaskar Chetnani, Alfonso Mondragón
A T-box regulator or riboswitch actively monitors the levels of charged/uncharged tRNA and participates in amino acid homeostasis by regulating genes involved in their utilization or biosynthesis. It has an aptamer domain for cognate tRNA recognition and an expression platform to sense the charge state and modulate gene expression. These two conserved domains are connected by a variable linker that harbors additional secondary structural elements, such as Stem III. The structural basis for specific tRNA binding is known, but the structural basis for charge sensing and the role of other elements remains elusive...
May 22, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28531104/stumbling-across-the-same-phage-comparative-genomics-of-widespread-temperate-phages-infecting-the-fish-pathogen-vibrio-anguillarum
#9
Panos G Kalatzis, Nanna Iben Rørbo, Daniel Castillo, Jesper Juel Mauritzen, Jóhanna Jørgensen, Constantina Kokkari, Faxing Zhang, Pantelis Katharios, Mathias Middelboe
Nineteen Vibrio anguillarum-specific temperate bacteriophages isolated across Europe and Chile from aquaculture and environmental sites were genome sequenced and analyzed for host range, morphology and life cycle characteristics. The phages were classified as Siphoviridae with genome sizes between 46,006 and 54,201 bp. All 19 phages showed high genetic similarity, and 13 phages were genetically identical. Apart from sporadically distributed single nucleotide polymorphisms (SNPs), genetic diversifications were located in three variable regions (VR1, VR2 and VR3) in six of the phage genomes...
May 20, 2017: Viruses
https://www.readbyqxmd.com/read/28529651/draft-genome-sequence-of-roseovarius-sp-a-2-an-iodide-oxidizing-bacterium-isolated-from-natural-gas-brine-water-chiba-japan
#10
Tri Yuliana, Nobuyoshi Nakajima, Shigeki Yamamura, Masaru Tomita, Haruo Suzuki, Seigo Amachi
Roseovarius sp. A-2 is a heterotrophic iodide (I(-))-oxidizing bacterium isolated from iodide-rich natural gas brine water in Chiba, Japan. This strain oxidizes iodide to molecular iodine (I2) by means of an extracellular multicopper oxidase. Here we report the draft genome sequence of strain A-2. The draft genome contained 46 tRNA genes, 1 copy of a 16S-23S-5S rRNA operon, and 4,514 protein coding DNA sequences, of which 1,207 (27%) were hypothetical proteins. The genome contained a gene encoding IoxA, a multicopper oxidase previously found to catalyze the oxidation of iodide in Iodidimonas sp...
2017: Journal of Genomics
https://www.readbyqxmd.com/read/28528473/properties-of-streptomyces-albus-j1074-mutant-deficient-in-trna-leu-uaa-gene-blda
#11
Oksana Koshla, Maria Lopatniuk, Ihor Rokytskyy, Oleksandr Yushchuk, Yuriy Dacyuk, Victor Fedorenko, Andriy Luzhetskyy, Bohdan Ostash
Streptomyces albus J1074 is one of the most popular and convenient hosts for heterologous expression of gene clusters directing the biosynthesis of various natural metabolic products, such as antibiotics. This fuels interest in elucidation of genetic mechanisms that may limit secondary metabolism in J1074. Here, we report the generation and initial study of J1074 mutant, deficient in gene bldA for tRNA(Leu)UAA, the only tRNA capable of decoding rare leucyl TTA codon in Streptomyces. The bldA deletion in J1074 resulted in a highly conditional Bld phenotype, with depleted formation of aerial hyphae on certain solid media...
May 20, 2017: Archives of Microbiology
https://www.readbyqxmd.com/read/28525745/conditional-switch-between-frameshifting-regimes-upon-translation-of-dnax-mrna
#12
Neva Caliskan, Ingo Wohlgemuth, Natalia Korniy, Michael Pearson, Frank Peske, Marina V Rodnina
Ribosome frameshifting during translation of bacterial dnaX can proceed via different routes, generating a variety of distinct polypeptides. Using kinetic experiments, we show that -1 frameshifting predominantly occurs during translocation of two tRNAs bound to the slippery sequence codons. This pathway depends on a stem-loop mRNA structure downstream of the slippery sequence and operates when aminoacyl-tRNAs are abundant. However, when aminoacyl-tRNAs are in short supply, the ribosome switches to an alternative frameshifting pathway that is independent of a stem-loop...
May 18, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28525744/ctf4-prevents-genome-rearrangements-by-suppressing-dna-double-strand-break-formation-and-its-end-resection-at-arrested-replication-forks
#13
Mariko Sasaki, Takehiko Kobayashi
Arrested replication forks lead to DNA double-strand breaks (DSBs), which are a major source of genome rearrangements. Yet DSB repair in the context of broken forks remains poorly understood. Here we demonstrate that DSBs that are formed at arrested forks in the budding yeast ribosomal RNA gene (rDNA) locus are normally repaired by pathways dependent on the Mre11-Rad50-Xrs2 complex but independent of HR. HR is also dispensable for DSB repair at stalled forks at tRNA genes. In contrast, in cells lacking the core replisome component Ctf4, DSBs are formed more frequently, and these DSBs undergo end resection and HR-mediated repair that is prone to rDNA hyper-amplification; this highlights Ctf4 as a key regulator of DSB end resection at arrested forks...
May 18, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28522991/brachyspira-hyodysenteriae-and-b-pilosicoli-proteins-recognized-by-sera-of-challenged-pigs
#14
Vanessa Casas, Arantza Rodríguez-Asiain, Roberto Pinto-Llorente, Santiago Vadillo, Montserrat Carrascal, Joaquin Abian
The spirochetes Brachyspira hyodysenteriae and B. pilosicoli are pig intestinal pathogens that are the causative agents of swine dysentery (SD) and porcine intestinal spirochaetosis (PIS), respectively. Although some inactivated bacterin and recombinant vaccines have been explored as prophylactic treatments against these species, no effective vaccine is yet available. Immunoproteomics approaches hold the potential for the identification of new, suitable candidates for subunit vaccines against SD and PIS. These strategies take into account the gene products actually expressed and present in the cells, and thus susceptible of being targets of immune recognition...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28522548/a-multi-purpose-toolkit-to-enable-advanced-genome-engineering-in-plants
#15
Tomas Cermak, Shaun J Curtin, Javier Gil-Humanes, Radim Čegan, Thomas J Y Kono, Eva Konečná, Joseph J Belanto, Colby G Starker, Jade W Mathre, Rebecca L Greenstein, Daniel F Voytas
We report a comprehensive toolkit that enables targeted, specific modification of monocot and dicot genomes using a variety of genome engineering approaches. Our reagents, based on TALENs and the CRISPR/Cas9 system, are systematized for fast, modular cloning and accommodate diverse regulatory sequences to drive reagent expression. Vectors are optimized to create either single or multiple gene knockouts and large chromosomal deletions. Moreover, integration of geminivirus-based vectors enables precise gene editing through homologous recombination...
May 18, 2017: Plant Cell
https://www.readbyqxmd.com/read/28516732/diadenosine-tetraphosphate-ap4a-an-e-coli-alarmone-or-a-damage-metabolite
#16
Dragana Despotović, Alexander Brandis, Alon Savidor, Yishai Levin, Laura Fumagalli, Dan S Tawfik
Under stress, metabolism is changing: specific up- or down-regulation of proteins and metabolites occurs as well as side-effects. Distinguishing specific stress-signaling metabolites (alarmones) from side-products (damage metabolites) is not trivial. One example is diadenosine tetraphosphate, Ap4A - a side-product of aminoacyl-tRNA synthetases found in all domains of life. The earliest observations suggested that Ap4A serves as an alarmone for heat stress in E. coli. However, despite 50 years of research, the signaling mechanisms associated with Ap4A remain unknown...
May 18, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28512204/the-human-rna-binding-protein-rbfa-promotes-the-maturation-of-the-mitochondrial-ribosome
#17
Agata Rozanska, Ricarda Richter-Dennerlein, Joanna Rorbach, Fei Gao, Richard J Lewis, Zofia M Chrzanowska-Lightowlers, Robert N Lightowlers
Accurate assembly and maturation of human mitochondrial ribosomes is essential for synthesis of the 13 polypeptides encoded by the mitochondrial genome. This process requires the correct integration of 80 proteins, 1 mt-tRNA and 2 mt-rRNA species, the latter being post-transcriptionally modified at a number of sites. Here, we report that human RBFA is a mitochondrial RNA-binding protein that exerts crucial roles in mitoribosome biogenesis. Unlike its bacterial orthologue, RBFA associates mainly with helix 44 and 45 of the 12S rRNA in the mitoribosomal small subunit to promote dimethylation of 2 highly conserved consecutive adenines...
May 16, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28511668/structural-similarities-and-functional-differences-clarify-evolutionary-relationships-between-trna-healing-enzymes-and-the-myelin-enzyme-cnpase
#18
Gopinath Muruganandam, Arne Raasakka, Matti Myllykoski, Inari Kursula, Petri Kursula
BACKGROUND: Eukaryotic tRNA splicing is an essential process in the transformation of a primary tRNA transcript into a mature functional tRNA molecule. 5'-phosphate ligation involves two steps: a healing reaction catalyzed by polynucleotide kinase (PNK) in association with cyclic phosphodiesterase (CPDase), and a sealing reaction catalyzed by an RNA ligase. The enzymes that catalyze tRNA healing in yeast and higher eukaryotes are homologous to the members of the 2H phosphoesterase superfamily, in particular to the vertebrate myelin enzyme 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase)...
May 16, 2017: BMC Biochemistry
https://www.readbyqxmd.com/read/28510592/alteration-of-protein-function-by-a-silent-polymorphism-linked-to-trna-abundance
#19
Sebastian Kirchner, Zhiwei Cai, Robert Rauscher, Nicolai Kastelic, Melanie Anding, Andreas Czech, Bertrand Kleizen, Lynda S Ostedgaard, Ineke Braakman, David N Sheppard, Zoya Ignatova
Synonymous single nucleotide polymorphisms (sSNPs) are considered neutral for protein function, as by definition they exchange only codons, not amino acids. We identified an sSNP that modifies the local translation speed of the cystic fibrosis transmembrane conductance regulator (CFTR), leading to detrimental changes to protein stability and function. This sSNP introduces a codon pairing to a low-abundance tRNA that is particularly rare in human bronchial epithelia, but not in other human tissues, suggesting tissue-specific effects of this sSNP...
May 2017: PLoS Biology
https://www.readbyqxmd.com/read/28506829/an-asymmetric-dimeric-structure-of-trmj-trna-methyltransferase-from-zymomonas-mobilis-with-a-flexible-c-terminal-dimer
#20
Do-Heon Gu, Mi-Young Park, Jeong-Sun Kim
The tRNA methyltransferase J (TrmJ) and D (TrmD) catalyze the transferring reaction of a methyl group to the tRNA anticodon loop. They commonly have the N-terminal domain (NTD) and the C-terminal domain (CTD). Whereas two monomeric CTDs symmetrically interact with a dimeric NTD in TrmD, a CTD dimer has exhibited an asymmetric interaction with the NTD dimer in the presence of a product. The elucidated apo-structure of the full-length TrmJ from Zymomonas mobilis ZM4 shows a dimeric CTD that asymmetrically interacts with the NTD dimer, thereby distributing non-symmetrical potential charge on the both side of the protein surface...
May 12, 2017: Biochemical and Biophysical Research Communications
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