The landscape of microbial phenotypic traits and associated genes
Bacteria and Archaea display a variety of phenotypic traits and can adapt to diverse ecological niches. However, systematic annotation of prokaryotic phenotypes is lacking. We have therefore developed ProTraits, a resource containing ~545 000 novel phenotype inferences, spanning 424 traits assigned to 3046 bacterial and archaeal species. These annotations were assigned by a computational pipeline that associates microbes with phenotypes by text-mining the scientific literature and the broader World Wide Web, while also being able to define novel concepts from unstructured text. Moreover, the ProTraits pipeline assigns phen...
Source: Nucleic Acids Research - December 1, 2016 Category: Research Authors: Brbic, M., Piskorec, M., Vidulin, V., Krisko, A., Smuc, T., Supek, F. Tags: Data Resources and Analyses Source Type: research
Localized structural frustration for evaluating the impact of sequence variants
Population-scale sequencing is increasingly uncovering large numbers of rare single-nucleotide variants (SNVs) in coding regions of the genome. The rarity of these variants makes it challenging to evaluate their deleteriousness with conventional phenotype–genotype associations. Protein structures provide a way of addressing this challenge. Previous efforts have focused on globally quantifying the impact of SNVs on protein stability. However, local perturbations may severely impact protein functionality without strongly disrupting global stability (e.g. in relation to catalysis or allostery). Here, we describe a workf...
Source: Nucleic Acids Research - December 1, 2016 Category: Research Authors: Kumar, S., Clarke, D., Gerstein, M. Tags: Computational Methods Computational Biology Source Type: research
Codon usage is less optimized in eukaryotic gene segments encoding intrinsically disordered regions than in those encoding structural domains
Codon usage tends to be optimized in highly expressed genes. A plausible explanation for this phenomenon is that translational accuracy is increased in highly expressed genes with infrequent use of rare codons. Besides structural domains (SDs), eukaryotic proteins generally have intrinsically disordered regions (IDRs) that by themselves do not assume unique three-dimensional structures. As IDRs are free from structural constraint, they can probably accommodate more translational errors than SDs can. Thus, codon usage in IDRs is likely to be less optimized than that in SDs. Codon usage in all the genes of seven eukaryotes w...
Source: Nucleic Acids Research - December 1, 2016 Category: Research Authors: Homma, K., Noguchi, T., Fukuchi, S. Tags: Computational Biology Source Type: research
Modification of orthogonal tRNAs: unexpected consequences for sense codon reassignment
Breaking the degeneracy of the genetic code via sense codon reassignment has emerged as a way to incorporate multiple copies of multiple non-canonical amino acids into a protein of interest. Here, we report the modification of a normally orthogonal tRNA by a host enzyme and show that this adventitious modification has a direct impact on the activity of the orthogonal tRNA in translation. We observed nearly equal decoding of both histidine codons, CAU and CAC, by an engineered orthogonal M. jannaschii tRNA with an AUG anticodon: tRNAOpt. We suspected a modification of the tRNAOptAUG anticodon was responsible for the anomalo...
Source: Nucleic Acids Research - December 1, 2016 Category: Research Authors: Biddle, W., Schmitt, M. A., Fisk, J. D. Tags: Chemical Biology and Nucleic Acid Chemistry Source Type: research
Light-induced oxidation of the telomeric G4 DNA in complex with Zn(II) tetracarboxymethyl porphyrin
Structure-specific ligands are convenient tools for the recognition, targeting or probing of non-canonical DNA structures. Porphyrin derivatives exhibit a preference for interaction with G-quadruplex (G4) structures over canonical duplex DNA and are able to cause photoinducible damage to nucleic acids. Here, we show that Zn(II) 5,10,15,20-tetrakis(N-carboxymethyl-4-pyridinium)porphyrin (ZnP1) interacts with different conformations of the telomeric sequence d(TAGGG(TTAGGG)3) at submicromolar concentrations without any detectible disturbance of the particular fold. Among different folds, potassium (3+1) hybrid G4-structure. ...
Source: Nucleic Acids Research - December 1, 2016 Category: Research Authors: Beniaminov, A. D., Novikov, R. A., Mamaeva, O. K., Mitkevich, V. A., Smirnov, I. P., Livshits, M. A., Shchyolkina, A. K., Kaluzhny, D. N. Tags: Chemical Biology and Nucleic Acid Chemistry Source Type: research
The multifaceted influence of histone deacetylases on DNA damage signalling and DNA repair
Histone/protein deacetylases play multiple roles in regulating gene expression and protein activation and stability. Their deregulation during cancer initiation and progression cause resistance to therapy. Here, we review the role of histone deacetylases (HDACs) and the NAD+ dependent sirtuins (SIRTs) in the DNA damage response (DDR). These lysine deacetylases contribute to DNA repair by base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR), non-homologous end joining (NHEJ), homologous recombination (HR) and interstrand crosslink (ICL) repair. Furthermore, we discuss possible mechanisms where...
Source: Nucleic Acids Research - December 1, 2016 Category: Research Authors: Roos, W. P., Krumm, A. Tags: SURVEY AND SUMMARY Source Type: research
Single molecule tracking of Ace1p in Saccharomyces cerevisiae defines a characteristic residence time for non-specific interactions of transcription factors with chromatin
In vivo single molecule tracking has recently developed into a powerful technique for measuring and understanding the transient interactions of transcription factors (TF) with their chromatin response elements. However, this method still lacks a solid foundation for distinguishing between specific and non-specific interactions. To address this issue, we took advantage of the power of molecular genetics of yeast. Yeast TF Ace1p has only five specific sites in the genome and thus serves as a benchmark to distinguish specific from non-specific binding. Here, we show that the estimated residence time of the short-residence mol...
Source: Nucleic Acids Research - December 1, 2016 Category: Research Authors: Ball, D. A., Mehta, G. D., Salomon-Kent, R., Mazza, D., Morisaki, T., Mueller, F., McNally, J. G., Karpova, T. S. Tags: Chromatin and Epigenetics, Transcriptome Mapping - Monitoring Gene Expression Methods Online Source Type: research
PAtCh-Cap: input strategy for improving analysis of ChIP-exo data sets and beyond
This reported method, termed protein attached chromatin capture (PAtCh-Cap), relies on the non-specific capture of chromatin-bound proteins via their carboxylate groups, leaving the DNA accessible for subsequent chemical treatments in parallel with chromatin separately immunoprecipitated for the target protein. Application of this input strategy not only significantly enhanced artifact removal from ChIP-exo data, increasing confidence in peak identification and allowing for de novo motif searching, but also afforded discovery of a novel CTCF binding motif. (Source: Nucleic Acids Research)
Source: Nucleic Acids Research - December 1, 2016 Category: Research Authors: Terooatea, T. W., Pozner, A., Buck-Koehntop, B. A. Tags: Chromatin and Epigenetics Methods Online Source Type: research
Single-nucleus RNA-seq of differentiating human myoblasts reveals the extent of fate heterogeneity
Myoblasts are precursor skeletal muscle cells that differentiate into fused, multinucleated myotubes. Current single-cell microfluidic methods are not optimized for capturing very large, multinucleated cells such as myotubes. To circumvent the problem, we performed single-nucleus transcriptome analysis. Using immortalized human myoblasts, we performed RNA-seq analysis of single cells (scRNA-seq) and single nuclei (snRNA-seq) and found them comparable, with a distinct enrichment for long non-coding RNAs (lncRNAs) in snRNA-seq. We then compared snRNA-seq of myoblasts before and after differentiation. We observed the presence...
Source: Nucleic Acids Research - December 1, 2016 Category: Research Authors: Zeng, W., Jiang, S., Kong, X., El-Ali, N., Ball, A. R., Ma, C. I.-H., Hashimoto, N., Yokomori, K., Mortazavi, A. Tags: Transcriptome Mapping - Monitoring Gene Expression Methods Online Source Type: research
An efficient system for selectively altering genetic information within mRNAs
Site-directed RNA editing (SDRE) is a strategy to precisely alter genetic information within mRNAs. By linking the catalytic domain of the RNA editing enzyme ADAR to an antisense guide RNA, specific adenosines can be converted to inosines, biological mimics for guanosine. Previously, we showed that a genetically encoded iteration of SDRE could target adenosines expressed in human cells, but not efficiently. Here we developed a reporter assay to quantify editing, and used it to improve our strategy. By enhancing the linkage between ADAR's catalytic domain and the guide RNA, and by introducing a mutation in the catalytic dom...
Source: Nucleic Acids Research - December 1, 2016 Category: Research Authors: Montiel-Gonzalez, M. F., Vallecillo-Viejo, I. C., Rosenthal, J. J. C. Tags: RNA characterisation and manipulation Methods Online Source Type: research
Analysis of C. elegans muscle transcriptome using trans-splicing-based RNA tagging (SRT)
Current approaches to profiling tissue-specific gene expression in C. elegans require delicate manipulation and are difficult under certain conditions, e.g. from dauer or aging worms. We have developed an easy and robust method for tissue-specific RNA-seq by taking advantage of the endogenous trans-splicing process. In this method, transgenic worms are generated in which a spliced leader (SL) RNA gene is fused with a sequence tag and driven by a tissue-specific promoter. Only in the tissue of interest, the tagged SL RNA gene is transcribed and then trans-spliced onto mRNAs. The tag allows enrichment and sequencing of mRNAs...
Source: Nucleic Acids Research - December 1, 2016 Category: Research Authors: Ma, X., Zhan, G., Sleumer, M. C., Chen, S., Liu, W., Zhang, M. Q., Liu, X. Tags: Transcriptome Mapping - Monitoring Gene Expression Methods Online Source Type: research
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(Source: Nucleic Acids Research)
Source: Nucleic Acids Research - December 1, 2016 Category: Research Tags: Front-Matter/Back-Matter Source Type: research
Nucleic Acids Research: Editorial Board
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Source: Nucleic Acids Research - December 1, 2016 Category: Research Tags: Front-Matter/Back-Matter Source Type: research
Nucleic Acids Research: VOLUME 44 ISSUE 21 2016
(Source: Nucleic Acids Research)
Source: Nucleic Acids Research - December 1, 2016 Category: Research Tags: Front-Matter/Back-Matter Source Type: research
A small protein inhibits proliferating cell nuclear antigen by breaking the DNA clamp
(Source: Nucleic Acids Research)
Source: Nucleic Acids Research - November 28, 2016 Category: Research Authors: Altieri, A. S., Ladner, J. E., Li, Z., Robinson, H., Sallman, Z. F., Marino, J. P., Kelman, Z. Tags: Corrigendum Source Type: research
