44,755 results match your criteria Nucleic acids research[Journal]


SAM68 interaction with U1A modulates U1 snRNP recruitment and regulates mTor pre-mRNA splicing.

Nucleic Acids Res 2019 Feb 15. Epub 2019 Feb 15.

Centre de recherche du CHU de Québec-Université Laval (axe Oncologie), Québec, QC G1R 3S3, Canada.

Src associated in mitosis (SAM68) plays major roles in regulating RNA processing events, such as alternative splicing and mRNA translation, implicated in several developmental processes. It was previously shown that SAM68 regulates the alternative splicing of the mechanistic target of rapamycin (mTor), but the mechanism regulating this process remains elusive. Here, we report that SAM68 interacts with U1 small nuclear ribonucleoprotein (U1 snRNP) to promote splicing at the 5' splice site in intron 5 of mTor. Read More

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http://dx.doi.org/10.1093/nar/gkz099DOI Listing
February 2019
2 Reads

CRISPR-assisted multi-dimensional regulation for fine-tuning gene expression in Bacillus subtilis.

Nucleic Acids Res 2019 Feb 15. Epub 2019 Feb 15.

State Key Laboratory of Biocatalysis and Enzyme Engineering, Hubei Collaborative Innovation Center for Green Transformation of Bio-resources, Hubei Key Laboratory of Industrial Biotechnology, School of Life Sciences, Hubei University, Wuhan, Hubei, China 430062.

Fine-tuning of gene expression is crucial for protein expression and pathway construction, but it still faces formidable challenges due to the hierarchical gene regulation at multiple levels in a context-dependent manner. In this study, we defined the optimal targeting windows for CRISPRa and CRISPRi of the dCas9-α/ω system, and demonstrated that this system could act as a single master regulator to simultaneously activate and repress the expression of different genes by designing position-specific gRNAs. The application scope of dCas9-ω was further expanded by a newly developed CRISPR-assisted Oligonucleotide Annealing based Promoter Shuffling (OAPS) strategy, which could generate a high proportion of functional promoter mutants and facilitate the construction of effective promoter libraries in microorganisms with low transformation efficiency. Read More

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http://dx.doi.org/10.1093/nar/gkz072DOI Listing
February 2019

Human H4 tail stimulates HIV-1 integration through binding to the carboxy-terminal domain of integrase.

Nucleic Acids Res 2019 Feb 15. Epub 2019 Feb 15.

Fundamental Microbiology and Pathogenicity Laboratory, UMR 5234 CNRS-University of Bordeaux, SFR TransBioMed. Bordeaux, France.

The integration of the retroviral genome into the chromatin of the infected cell is catalysed by the integrase (IN)•viral DNA complex (intasome). This process requires functional association between the integration complex and the nucleosomes. Direct intasome/histone contacts have been reported to modulate the interaction between the integration complex and the target DNA (tDNA). Read More

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http://dx.doi.org/10.1093/nar/gkz091DOI Listing
February 2019

Engineering of a thermostable viral polymerase using metagenome-derived diversity for highly sensitive and specific RT-PCR.

Nucleic Acids Res 2019 Feb 15. Epub 2019 Feb 15.

Department of Research and Development, QIAGEN Beverly, 100 Cummings Center, Suite 407J, Beverly, MA 01915, USA.

Reverse transcription is an essential initial step in the analysis of RNA for most PCR-based amplification and detection methods. Despite advancements in these technologies, efficient conversion of RNAs that form stable secondary structures and double-stranded RNA targets remains challenging as retroviral-derived reverse transcriptases are often not sufficiently thermostable to catalyze synthesis at temperatures high enough to completely relax these structures. Here we describe the engineering and improvement of a thermostable viral family A polymerase with inherent reverse transcriptase activity for use in RT-PCR. Read More

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http://dx.doi.org/10.1093/nar/gkz104DOI Listing
February 2019

Recycling of single-stranded DNA-binding protein by the bacterial replisome.

Nucleic Acids Res 2019 Feb 15. Epub 2019 Feb 15.

Molecular Horizons and School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, New South Wales 2522, Australia.

Single-stranded DNA-binding proteins (SSBs) support DNA replication by protecting single-stranded DNA from nucleolytic attack, preventing intra-strand pairing events and playing many other regulatory roles within the replisome. Recent developments in single-molecule approaches have led to a revised picture of the replisome that is much more complex in how it retains or recycles protein components. Here, we visualize how an in vitro reconstituted Escherichia coli replisome recruits SSB by relying on two different molecular mechanisms. Read More

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http://dx.doi.org/10.1093/nar/gkz090DOI Listing
February 2019
6 Reads

Selective recognition of c-MYC Pu22 G-quadruplex by a fluorescent probe.

Nucleic Acids Res 2019 Feb 13. Epub 2019 Feb 13.

State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, PR China.

Nucleic acid mimics of fluorescent proteins can be valuable tools to locate and image functional biomolecules in cells. Stacking between the internal G-quartet, formed in the mimics, and the exogenous fluorophore probes constitutes the basis for fluorescence emission. The precision of recognition depends upon probes selectively targeting the specific G-quadruplex in the mimics. Read More

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http://dx.doi.org/10.1093/nar/gkz059DOI Listing
February 2019

Modulation of the ATM/autophagy pathway by a G-quadruplex ligand tips the balance between senescence and apoptosis in cancer cells.

Nucleic Acids Res 2019 Feb 13. Epub 2019 Feb 13.

Institut Bergonié, Université de Bordeaux, INSERM U1218, F-33076 Bordeaux, France.

G-quadruplex ligands exert their antiproliferative effects through telomere-dependent and telomere-independent mechanisms, but the inter-relationships among autophagy, cell growth arrest and cell death induced by these ligands remain largely unexplored. Here, we demonstrate that the G-quadruplex ligand 20A causes growth arrest of cancer cells in culture and in a HeLa cell xenografted mouse model. This response is associated with the induction of senescence and apoptosis. Read More

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https://academic.oup.com/nar/advance-article/doi/10.1093/nar
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http://dx.doi.org/10.1093/nar/gkz095DOI Listing
February 2019
1 Read

Role of Cdc23/Mcm10 in generating the ribonucleotide imprint at the mat1 locus in fission yeast.

Nucleic Acids Res 2019 Feb 13. Epub 2019 Feb 13.

Institute of Microbial Technology, Sector 39A, Chandigarh 160036, India.

The developmental asymmetry of fission yeast daughter cells derives from inheriting 'older Watson' versus 'older Crick' DNA strand from the parental cell, strands that are complementary but not identical with each other. A novel DNA strand-specific 'imprint', installed during DNA replication at the mating-type locus (mat1), imparts competence for cell type inter-conversion to one of the two chromosome replicas. The catalytic subunit of DNA Polymerase α (Polα) has been implicated in the imprinting process. Read More

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http://dx.doi.org/10.1093/nar/gkz092DOI Listing
February 2019

Structural organization of a Type III-A CRISPR effector subcomplex determined by X-ray crystallography and cryo-EM.

Nucleic Acids Res 2019 Feb 13. Epub 2019 Feb 13.

Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA.

Clustered regularly interspaced short palindromic repeats (CRISPR) and their associated Cas proteins provide an immune-like response in many prokaryotes against extraneous nucleic acids. CRISPR-Cas systems are classified into different classes and types. Class 1 CRISPR-Cas systems form multi-protein effector complexes that includes a guide RNA (crRNA) used to identify the target for destruction. Read More

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http://dx.doi.org/10.1093/nar/gkz079DOI Listing
February 2019

TDP-43 regulates site-specific 2'-O-methylation of U1 and U2 snRNAs via controlling the Cajal body localization of a subset of C/D scaRNAs.

Nucleic Acids Res 2019 Feb 13. Epub 2019 Feb 13.

Department of Applied Biological Science and Global Innovation Research Organizations, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo 183-8509, Japan.

TDP-43 regulates cellular levels of Cajal bodies (CBs) that provide platforms for the assembly and RNA modifications of small nuclear ribonucleoproteins (snRNPs) involved in pre-mRNA splicing. Alterations in these snRNPs may be linked to pathogenesis of amyotrophic lateral sclerosis. However, specific roles for TDP-43 in CBs remain unknown. Read More

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http://dx.doi.org/10.1093/nar/gkz086DOI Listing
February 2019
1 Read

Structural variation and fusion detection using targeted sequencing data from circulating cell free DNA.

Nucleic Acids Res 2019 Feb 13. Epub 2019 Feb 13.

Department of Urologic Sciences, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia V52 1M9, Canada.

Motivation: Cancer is a complex disease that involves rapidly evolving cells, often forming multiple distinct clones. In order to effectively understand progression of a patient-specific tumor, one needs to comprehensively sample tumor DNA at multiple time points, ideally obtained through inexpensive and minimally invasive techniques. Current sequencing technologies make the 'liquid biopsy' possible, which involves sampling a patient's blood or urine and sequencing the circulating cell free DNA (cfDNA). Read More

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http://dx.doi.org/10.1093/nar/gkz067DOI Listing
February 2019

Delivering SaCas9 mRNA by lentivirus-like bionanoparticles for transient expression and efficient genome editing.

Nucleic Acids Res 2019 Feb 13. Epub 2019 Feb 13.

Wake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences, Winston-Salem, NC, USA.

The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) system discovered using bacteria has been repurposed for genome editing in human cells. Transient expression of the editor proteins (e.g. Read More

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http://dx.doi.org/10.1093/nar/gkz093DOI Listing
February 2019

Understanding the role of intermolecular interactions between lissoclimides and the eukaryotic ribosome.

Nucleic Acids Res 2019 Feb 13. Epub 2019 Feb 13.

Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U964, CNRS UMR7104, Université de Strasbourg, 67404 Illkirch, France.

Natural products that target the eukaryotic ribosome are promising therapeutics to treat a variety of cancers. It is therefore essential to determine their molecular mechanism of action to fully understand their mode of interaction with the target and to inform the development of new synthetic compounds with improved potency and reduced cytotoxicity. Toward this goal, we have previously established a short synthesis pathway that grants access to multiple congeners of the lissoclimide family. Read More

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http://dx.doi.org/10.1093/nar/gkz053DOI Listing
February 2019

Set1-catalyzed H3K4 trimethylation antagonizes the HIR/Asf1/Rtt106 repressor complex to promote histone gene expression and chronological life span.

Nucleic Acids Res 2019 Feb 13. Epub 2019 Feb 13.

State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan, Hubei 430062, China.

Aging is the main risk factor for many prevalent diseases. However, the molecular mechanisms regulating aging at the cellular level are largely unknown. Using single cell yeast as a model organism, we found that reducing yeast histone proteins accelerates chronological aging and increasing histone supply extends chronological life span. Read More

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http://dx.doi.org/10.1093/nar/gkz101DOI Listing
February 2019
1 Read

DeepRibo: a neural network for precise gene annotation of prokaryotes by combining ribosome profiling signal and binding site patterns.

Nucleic Acids Res 2019 Feb 8. Epub 2019 Feb 8.

KERMIT, Department of Data Analysis and Mathematical Modelling, Ghent University, Coupure Links 653, 9000 Gent, Belgium.

Annotation of gene expression in prokaryotes often finds itself corrected due to small variations of the annotated gene regions observed between different (sub)-species. It has become apparent that traditional sequence alignment algorithms, used for the curation of genomes, are not able to map the full complexity of the genomic landscape. We present DeepRibo, a novel neural network utilizing features extracted from ribosome profiling information and binding site sequence patterns that shows to be a precise tool for the delineation and annotation of expressed genes in prokaryotes. Read More

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http://dx.doi.org/10.1093/nar/gkz061DOI Listing
February 2019

Delineation of pentatricopeptide repeat codes for target RNA prediction.

Nucleic Acids Res 2019 Feb 11. Epub 2019 Feb 11.

National Key Laboratory of Crop Genetic Improvement and National Centre of Plant Gene Research, Huazhong Agricultural University, Wuhan 430070, China.

Members of the pentatricopeptide repeat (PPR) protein family are sequence-specific RNA-binding proteins that play crucial roles in organelle RNA metabolism. Each PPR protein consists of a tandem array of PPR motifs, each of which aligns to one nucleotide of the RNA target. The di-residues in the PPR motif, which are referred to as the PPR codes, determine nucleotide specificity. Read More

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http://dx.doi.org/10.1093/nar/gkz075DOI Listing
February 2019
1 Read

Loss of RNA-binding protein GRSF1 activates mTOR to elicit a proinflammatory transcriptional program.

Nucleic Acids Res 2019 Feb 11. Epub 2019 Feb 11.

Laboratory of Genetics and Genomics, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, MD, USA.

The RNA-binding protein GRSF1 (G-rich RNA sequence-binding factor 1) critically maintains mitochondrial homeostasis. Accordingly, loss of GRSF1 impaired mitochondrial respiration and increased the levels of reactive oxygen species (ROS), triggering DNA damage, growth suppression, and a senescent phenotype characterized by elevated production and secretion of interleukin (IL)6. Here, we characterize the pathways that govern IL6 production in response to mitochondrial dysfunction in GRSF1-depleted cells. Read More

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http://dx.doi.org/10.1093/nar/gkz082DOI Listing
February 2019

Structural basis of ubiquitin recognition by the winged-helix domain of Cockayne syndrome group B protein.

Nucleic Acids Res 2019 Feb 11. Epub 2019 Feb 11.

Institute for Quantitative Biosciences, The University of Tokyo, Tokyo 113-0032, Japan.

Cockayne syndrome group B (CSB, also known as ERCC6) protein is involved in many DNA repair processes and essential for transcription-coupled repair (TCR). The central region of CSB has the helicase motif, whereas the C-terminal region contains important regulatory elements for repair of UV- and oxidative stress-induced damages and double-strand breaks (DSBs). A previous study suggested that a small part (∼30 residues) within this region was responsible for binding to ubiquitin (Ub). Read More

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http://dx.doi.org/10.1093/nar/gkz081DOI Listing
February 2019

CPPred: coding potential prediction based on the global description of RNA sequence.

Nucleic Acids Res 2019 Feb 11. Epub 2019 Feb 11.

School of Physics, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China.

The rapid and accurate approach to distinguish between coding RNAs and ncRNAs has been playing a critical role in analyzing thousands of novel transcripts, which have been generated in recent years by next-generation sequencing technology. Previously developed methods CPAT, CPC2 and PLEK can distinguish coding RNAs and ncRNAs very well, but poorly distinguish between small coding RNAs and small ncRNAs. Herein, we report an approach, CPPred (coding potential prediction), which is based on SVM classifier and multiple sequence features including novel RNA features encoded by the global description. Read More

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http://dx.doi.org/10.1093/nar/gkz087DOI Listing
February 2019

Genetic screens reveal mechanisms for the transcriptional regulation of tissue-specific genes in normal cells and tumors.

Nucleic Acids Res 2019 Feb 7. Epub 2019 Feb 7.

Univ. Paris Diderot, Sorbonne Paris Cité, Epigenetics and Cell Fate, UMR 7216 CNRS, 75013 Paris, France.

The proper tissue-specific regulation of gene expression is essential for development and homeostasis in metazoans. However, the illegitimate expression of normally tissue-restricted genes-like testis- or placenta-specific genes-is frequently observed in tumors; this promotes transformation, but also allows immunotherapy. Two important questions are: how is the expression of these genes controlled in healthy cells? And how is this altered in cancer? To address these questions, we used an unbiased approach to test the ability of 350 distinct genetic or epigenetic perturbations to induce the illegitimate expression of over 40 tissue-restricted genes in primary human cells. Read More

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http://dx.doi.org/10.1093/nar/gkz080DOI Listing
February 2019

ChIAPoP: a new tool for ChIA-PET data analysis.

Nucleic Acids Res 2019 Feb 8. Epub 2019 Feb 8.

Division of Biostatistics and Bioinformatics, Department of Environmental Health, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA.

Chromatin Interaction Analysis by Paired-End Tag Sequencing (ChIA-PET) is a popular assay method for studying genome-wide chromatin interactions mediated by a protein of interest. The main goal of ChIA-PET data analysis is to detect interactions between DNA regions. Here, we propose a new method and the associated data analysis pipeline, ChIAPoP, to detect chromatin interactions from ChIA-PET data. Read More

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http://dx.doi.org/10.1093/nar/gkz062DOI Listing
February 2019

Validation of the nearest-neighbor model for Watson-Crick self-complementary DNA duplexes in molecular crowding condition.

Nucleic Acids Res 2019 Feb 8. Epub 2019 Feb 8.

Frontier Institute for Biomolecular Engineering Research (FIBER), Konan University, 7-1-20 Minatojima-Minamimachi, Chuo-ku, Kobe, 650-0047, Japan.

Recent advancement in nucleic acid techniques inside cells demands the knowledge of the stability of nucleic acid structures in molecular crowding. The nearest-neighbor model has been successfully used to predict thermodynamic parameters for the formation of nucleic acid duplexes, with significant accuracy in a dilute solution. However, knowledge about the applicability of the model in molecular crowding is still limited. Read More

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http://dx.doi.org/10.1093/nar/gkz071DOI Listing
February 2019

The E3-ligases SCFPpa and APC/CCdh1 co-operate to regulate CENP-ACID expression across the cell cycle.

Nucleic Acids Res 2019 Feb 8. Epub 2019 Feb 8.

Institute of Molecular Biology of Barcelona, IBMB, CSIC. Baldiri Reixac 4. 08028 Barcelona, Spain.

Centromere identity is determined by the specific deposition of CENP-A, a histone H3 variant localizing exclusively at centromeres. Increased CENP-A expression, which is a frequent event in cancer, causes mislocalization, ectopic kinetochore assembly and genomic instability. Proteolysis regulates CENP-A expression and prevents its misincorporation across chromatin. Read More

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http://dx.doi.org/10.1093/nar/gkz060DOI Listing
February 2019

C3P3-G1: first generation of a eukaryotic artificial cytoplasmic expression system.

Nucleic Acids Res 2019 Feb 6. Epub 2019 Feb 6.

Medical Microbiology and Immunology, University of Alberta, 6-142J Katz Group Centre for Pharmacy and Health Research, 114 Street NW, Edmonton, Alberta T6G 2E1, Canada.

Most eukaryotic expression systems make use of host-cell nuclear transcriptional and post-transcriptional machineries. Here, we present the first generation of the chimeric cytoplasmic capping-prone phage polymerase (C3P3-G1) expression system developed by biological engineering, which generates capped and polyadenylated transcripts in host-cell cytoplasm by means of two components. First, an artificial single-unit chimeric enzyme made by fusing an mRNA capping enzyme and a DNA-dependent RNA polymerase. Read More

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http://dx.doi.org/10.1093/nar/gkz069DOI Listing
February 2019
2 Reads

Multiple covalent fluorescence labeling of eukaryotic mRNA at the poly(A) tail enhances translation and can be performed in living cells.

Nucleic Acids Res 2019 Feb 6. Epub 2019 Feb 6.

Institute of Biochemistry, University of Münster, Wilhelm-Klemm-Straße 2, 48149 Münster, Germany.

Post-transcriptional regulation of gene expression occurs by multiple mechanisms, including subcellular localization of mRNA and alteration of the poly(A) tail length. These mechanisms play crucial roles in the dynamics of cell polarization and embryonic development. Furthermore, mRNAs are emerging therapeutics and chemical alterations to increase their translational efficiency are highly sought after. Read More

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http://dx.doi.org/10.1093/nar/gkz084DOI Listing
February 2019

MiRNA-891a-5p mediates HIV-1 Tat and KSHV Orf-K1 synergistic induction of angiogenesis by activating NF-κB signaling.

Nucleic Acids Res 2019 Feb 6. Epub 2019 Feb 6.

State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, P.R. China.

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http://dx.doi.org/10.1093/nar/gkz088DOI Listing
February 2019
3 Reads

Structural basis for DNA recognition by FOXC2.

Nucleic Acids Res 2019 Feb 5. Epub 2019 Feb 5.

NHC Key Laboratory of Cancer Proteomics and Laboratory of Structural Biology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.

The FOXC family of transcription factors (FOXC1 and FOXC2) plays essential roles in the regulation of embryonic, ocular, and cardiac development. Mutations and abnormal expression of FOXC proteins are implicated in genetic diseases as well as cancer. In this study, we determined two crystal structures of the DNA-binding domain (DBD) of human FOXC2 protein, in complex with different DNA sites. Read More

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http://dx.doi.org/10.1093/nar/gkz077DOI Listing
February 2019
2 Reads
9.112 Impact Factor

EnsembleCNV: an ensemble machine learning algorithm to identify and genotype copy number variation using SNP array data.

Nucleic Acids Res 2019 Feb 5. Epub 2019 Feb 5.

Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

The associations between diseases/traits and copy number variants (CNVs) have not been systematically investigated in genome-wide association studies (GWASs), primarily due to a lack of robust and accurate tools for CNV genotyping. Herein, we propose a novel ensemble learning framework, ensembleCNV, to detect and genotype CNVs using single nucleotide polymorphism (SNP) array data. EnsembleCNV (a) identifies and eliminates batch effects at raw data level; (b) assembles individual CNV calls into CNV regions (CNVRs) from multiple existing callers with complementary strengths by a heuristic algorithm; (c) re-genotypes each CNVR with local likelihood model adjusted by global information across multiple CNVRs; (d) refines CNVR boundaries by local correlation structure in copy number intensities; (e) provides direct CNV genotyping accompanied with confidence score, directly accessible for downstream quality control and association analysis. Read More

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https://academic.oup.com/nar/advance-article/doi/10.1093/nar
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http://dx.doi.org/10.1093/nar/gkz068DOI Listing
February 2019
2 Reads

The WD40 domain of FBXW7 is a poly(ADP-ribose)-binding domain that mediates the early DNA damage response.

Nucleic Acids Res 2019 Feb 5. Epub 2019 Feb 5.

Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.

FBXW7, a classic tumor suppressor, is a substrate recognition subunit of the Skp1-cullin-F-box (SCF) ubiquitin ligase that targets oncoproteins for ubiquitination and degradation. We recently found that FBXW7 is recruited to DNA damage sites to facilitate nonhomologous end-joining (NHEJ). The detailed underlying molecular mechanism, however, remains elusive. Read More

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http://dx.doi.org/10.1093/nar/gkz058DOI Listing
February 2019

Alternative conformation induced by substrate binding for Arabidopsis thaliana N6-methyl-AMP deaminase.

Authors:
Qian Jia Wei Xie

Nucleic Acids Res 2019 Feb 5. Epub 2019 Feb 5.

MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory for Biocontrol, School of Life Sciences, The Sun Yat-Sen University, Guangzhou, Guangdong, 510006, People's Republic of China.

Adenosine deaminase is involved in adenosine degradation and salvage pathway, and plays important physiological roles in purine metabolism. Recently, a novel type of adenosine deaminase-like protein has been identified, which displays deamination activity toward N6-methyl-adenosine monophosphate but not adenosine or AMP, and was consequently named N6-methyl-AMP deaminase (MAPDA). The underlying structural basis of MAPDA recognition and catalysis is poorly understood. Read More

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https://academic.oup.com/nar/advance-article/doi/10.1093/nar
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http://dx.doi.org/10.1093/nar/gkz070DOI Listing
February 2019
2 Reads

LncBook: a curated knowledgebase of human long non-coding RNAs.

Nucleic Acids Res 2019 Jan 31. Epub 2019 Jan 31.

BIG Data Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.

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http://dx.doi.org/10.1093/nar/gkz073DOI Listing
January 2019

Deficiency of the Fanconi anemia E2 ubiqitin conjugase UBE2T only partially abrogates Alu-mediated recombination in a new model of homology dependent recombination.

Nucleic Acids Res 2019 Feb 1. Epub 2019 Feb 1.

Department of Biochemistry and Molecular Biology, Boonshoft School of Medicine, Wright State University, Dayton, OH, USA.

The primary function of the UBE2T ubiquitin conjugase is in the monoubiquitination of the FANCI-FANCD2 heterodimer, a central step in the Fanconi anemia (FA) pathway. Genetic inactivation of UBE2T is responsible for the phenotypes of FANCT patients; however, a FANCT patient carrying a maternal duplication and a paternal deletion in the UBE2T loci displayed normal peripheral blood counts and UBE2T protein levels in B-lymphoblast cell lines. To test whether reversion by recombination between UBE2T AluYa5 elements could have occurred in the patient's hematopoietic stem cells despite the defects in homologous recombination (HR) in FA cells, we constructed HeLa cell lines containing the UBE2T AluYa5 elements and neighboring intervening sequences flanked by fluorescent reporter genes. Read More

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http://dx.doi.org/10.1093/nar/gkz026DOI Listing
February 2019

Cationic porphyrins with large side arm substituents as resonance light scattering ratiometric probes for specific recognition of nucleic acid G-quadruplexes.

Nucleic Acids Res 2019 Feb 4. Epub 2019 Feb 4.

Tianjin Key Laboratory of Biosensing and Molecular Recognition, College of Chemistry, Nankai University, Tianjin 300071, China.

Specific G-quadruplex-probing is crucial for both biological sciences and biosensing applications. Most reported probes are focused on fluorescent or colorimetric recognition of G-quadruplexes. Herein, for the first time, we reported a new specific G-quadruplex-probing technique-resonance light scattering (RLS)-based ratiometric recognition. Read More

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http://dx.doi.org/10.1093/nar/gkz064DOI Listing
February 2019

Systematic investigation of sequence requirements for DNA i-motif formation.

Nucleic Acids Res 2019 Feb 1. Epub 2019 Feb 1.

Institute of Biophysics of the Czech Academy of Sciences, v.v.i., Královopolská 135, 612 65 Brno, Czech Republic.

The formation of intercalated motifs (iMs) - secondary DNA structures based on hemiprotonated C.C+ pairs in suitable cytosine-rich DNA sequences, is reflected by typical changes in CD and UV absorption spectra. By means of spectroscopic methods, electrophoresis, chemical modifications and other procedures, we characterized iM formation and stability in sequences with different cytosine block lengths interrupted by various numbers and types of nucleotides. Read More

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http://dx.doi.org/10.1093/nar/gkz046DOI Listing
February 2019

Mitochondrial RNA granules are critically dependent on mtDNA replication factors Twinkle and mtSSB.

Nucleic Acids Res 2019 Feb 1. Epub 2019 Feb 1.

Radboud Center for Mitochondrial Medicine, Department of Paediatrics, Radboudumc, Nijmegen, The Netherlands.

Newly synthesized mitochondrial RNA is concentrated in structures juxtaposed to nucleoids, called RNA granules, that have been implicated in mitochondrial RNA processing and ribosome biogenesis. Here we show that two classical mtDNA replication factors, the mtDNA helicase Twinkle and single-stranded DNA-binding protein mtSSB, contribute to RNA metabolism in mitochondria and to RNA granule biology. Twinkle colocalizes with both mitochondrial RNA granules and nucleoids, and it can serve as bait to greatly enrich established RNA granule proteins, such as G-rich sequence factor 1, GRSF1. Read More

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http://dx.doi.org/10.1093/nar/gkz047DOI Listing
February 2019

FACT subunit Spt16 controls UVSSA recruitment to lesion-stalled RNA Pol II and stimulates TC-NER.

Nucleic Acids Res 2019 Feb 4. Epub 2019 Feb 4.

Department of Molecular Genetics, Oncode Institute, Erasmus MC, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.

Transcription-coupled nucleotide excision repair (TC-NER) is a dedicated DNA repair pathway that removes transcription-blocking DNA lesions (TBLs). TC-NER is initiated by the recognition of lesion-stalled RNA Polymerase II by the joint action of the TC-NER factors Cockayne Syndrome protein A (CSA), Cockayne Syndrome protein B (CSB) and UV-Stimulated Scaffold Protein A (UVSSA). However, the exact recruitment mechanism of these factors toward TBLs remains elusive. Read More

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http://dx.doi.org/10.1093/nar/gkz055DOI Listing
February 2019

Characterization of a metazoan ADA acetyltransferase complex.

Nucleic Acids Res 2019 Jan 31. Epub 2019 Jan 31.

Stowers Institute for Medical Research, Kansas City, MO 64110, USA.

The Gcn5 acetyltransferase functions in multiple acetyltransferase complexes in yeast and metazoans. Yeast Gcn5 is part of the large SAGA (Spt-Ada-Gcn5 acetyltransferase) complex and a smaller ADA acetyltransferase complex. In flies and mammals, Gcn5 (and its homolog pCAF) is part of various versions of the SAGA complex and another large acetyltransferase complex, ATAC (Ada2A containing acetyltransferase complex). Read More

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http://dx.doi.org/10.1093/nar/gkz042DOI Listing
January 2019

The Nup84 complex coordinates the DNA damage response to warrant genome integrity.

Nucleic Acids Res 2019 Feb 4. Epub 2019 Feb 4.

Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Universidad de Sevilla-CSIC-Universidad Pablo de Olavide, 41092 Seville, Spain.

DNA lesions interfere with cellular processes such as transcription and replication and need to be adequately resolved to warrant genome integrity. Beyond their primary role in molecule transport, nuclear pore complexes (NPCs) function in other processes such as transcription, nuclear organization and DNA double strand break (DSB) repair. Here we found that the removal of UV-induced DNA lesions by nucleotide excision repair (NER) is compromised in the absence of the Nup84 nuclear pore component. Read More

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http://dx.doi.org/10.1093/nar/gkz066DOI Listing
February 2019

RNA surveillance by uridylation-dependent RNA decay in Schizosaccharomyces pombe.

Nucleic Acids Res 2019 Feb 1. Epub 2019 Feb 1.

Department of Biochemistry, The University of Western Ontario, 1151 Richmond Street, London, ON N6A 5C1, Canada.

Uridylation-dependent RNA decay is a widespread eukaryotic pathway modulating RNA homeostasis. Terminal uridylyltransferases (Tutases) add untemplated uridyl residues to RNA 3'-ends, marking them for degradation by the U-specific exonuclease Dis3L2. In Schizosaccharomyces pombe, Cid1 uridylates a variety of RNAs. Read More

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https://academic.oup.com/nar/advance-article/doi/10.1093/nar
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http://dx.doi.org/10.1093/nar/gkz043DOI Listing
February 2019
3 Reads

SpyCLIP: an easy-to-use and high-throughput compatible CLIP platform for the characterization of protein-RNA interactions with high accuracy.

Nucleic Acids Res 2019 Jan 31. Epub 2019 Jan 31.

State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences; University of Chinese Academy of Sciences, Shanghai, China.

UV crosslinking and immunoprecipitation (CLIP) coupled with high-throughput sequencing is the most state-of-the-art technology to characterize protein-RNA interactions, yet only a small portion of RNA-binding proteins (RBPs) have been studied by CLIP due to its complex procedures and high level of false-positive signals. Herein, we report a SpyCLIP method that employs a covalent linkage formed between the RBP-fused SpyTag and SpyCatcher, which can withstand the harshest washing conditions for removing nonspecific interactions. Moreover, SpyCLIP circumvents the radioactive labeling and PAGE-membrane purification steps, and the whole procedure can be performed on beads and is readily amenable to automation. Read More

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http://dx.doi.org/10.1093/nar/gkz049DOI Listing
January 2019
1 Read
9.112 Impact Factor

PrimPol is required for the maintenance of efficient nuclear and mitochondrial DNA replication in human cells.

Nucleic Acids Res 2019 Jan 31. Epub 2019 Jan 31.

Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9RQ, UK.

Eukaryotic Primase-Polymerase (PrimPol) is an enzyme that maintains efficient DNA duplication by repriming replication restart downstream of replicase stalling lesions and structures. To elucidate the cellular requirements for PrimPol in human cells, we generated PrimPol-deleted cell lines and show that it plays key roles in maintaining active replication in both the nucleus and mitochondrion, even in the absence of exogenous damage. Human cells lacking PrimPol exhibit delayed recovery after UV-C damage and increased mutation frequency, micronuclei and sister chromatin exchanges but are not sensitive to genotoxins. Read More

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http://dx.doi.org/10.1093/nar/gkz056DOI Listing
January 2019

SAMURAI (Solid-phase Assisted Mutagenesis by Uracil Restriction for Accurate Integration) for antibody affinity maturation and paratope mapping.

Nucleic Acids Res 2019 Jan 31. Epub 2019 Jan 31.

KTH - Royal Institute of Technology, Department of Protein Science, 106 91 Stockholm, Sweden.

Mutagenesis libraries are essential for combinatorial protein engineering. Despite improvements in gene synthesis and directed mutagenesis, current methodologies still have limitations regarding the synthesis of complete antibody single-chain variable fragment (scFv) genes and simultaneous diversification of all six CDRs. Here, we describe the generation of mutagenesis libraries for antibody affinity maturation using a cell-free solid-phase technique for annealing of single-strand mutagenic oligonucleotides. Read More

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https://academic.oup.com/nar/advance-article/doi/10.1093/nar
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http://dx.doi.org/10.1093/nar/gkz050DOI Listing
January 2019
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Queuine links translational control in eukaryotes to a micronutrient from bacteria.

Nucleic Acids Res 2019 Feb 1. Epub 2019 Feb 1.

Institut für Biologie, Molekulare Zellbiologie, Humboldt-Universität zu Berlin, Berlin, Germany.

In eukaryotes, the wobble position of tRNA with a GUN anticodon is modified to the 7-deaza-guanosine derivative queuosine (Q34), but the original source of Q is bacterial, since Q is synthesized by eubacteria and salvaged by eukaryotes for incorporation into tRNA. Q34 modification stimulates Dnmt2/Pmt1-dependent C38 methylation (m5C38) in the tRNAAsp anticodon loop in Schizosaccharomyces pombe. Here, we show by ribosome profiling in S. Read More

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http://dx.doi.org/10.1093/nar/gkz063DOI Listing
February 2019

RNase H sequence preferences influence antisense oligonucleotide efficiency.

Nucleic Acids Res 2019 Jan 31. Epub 2019 Jan 31.

Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, DK-2200 Copenhagen N, Denmark.

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http://dx.doi.org/10.1093/nar/gkz065DOI Listing
January 2019

Thermodynamic characterization and nearest neighbor parameters for RNA duplexes under molecular crowding conditions.

Nucleic Acids Res 2019 Jan 30. Epub 2019 Jan 30.

Department of Chemistry, Saint Louis University, Saint Louis, MO 63103, USA.

It is essential to study RNA under molecular crowding conditions to better predict secondary structures of RNAs in vivo. No systematic study has been completed to determine the effects of molecular crowding on RNA duplexes of varying lengths and sequence composition. Here, optical melting, circular dichroism, and osmometry data were collected for RNA duplexes in a 20% polyethylene glycol (with an average molecular weight of 200 g/mol) solution (PEG 200), and nearest neighbor parameters were derived using this data. Read More

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http://dx.doi.org/10.1093/nar/gkz019DOI Listing
January 2019
2 Reads

Short tandem repeat stutter model inferred from direct measurement of in vitro stutter noise.

Nucleic Acids Res 2019 Jan 30. Epub 2019 Jan 30.

Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 761001, Israel.

Short tandem repeats (STRs) are polymorphic genomic loci valuable for various applications such as research, diagnostics and forensics. However, their polymorphic nature also introduces noise during in vitro amplification, making them difficult to analyze. Although it is possible to overcome stutter noise by using amplification-free library preparation, such protocols are presently incompatible with single cell analysis and with targeted-enrichment protocols. Read More

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http://dx.doi.org/10.1093/nar/gky1318DOI Listing
January 2019
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Dysregulation of the cohesin subunit RAD21 by Hepatitis C virus mediates host-virus interactions.

Nucleic Acids Res 2019 Jan 30. Epub 2019 Jan 30.

Molecular Virology Lab, Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel.

Hepatitis C virus (HCV) infection is the leading cause of chronic hepatitis, which often results in liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC). HCV possesses an RNA genome and its replication is confined to the cytoplasm. Yet, infection with HCV leads to global changes in gene expression, and chromosomal instability (CIN) in the host cell. Read More

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http://dx.doi.org/10.1093/nar/gkz052DOI Listing
January 2019
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The prokaryotic Argonaute proteins enhance homology sequence-directed recombination in bacteria.

Nucleic Acids Res 2019 Jan 30. Epub 2019 Jan 30.

State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China.

Argonaute proteins are present and conserved in all domains of life. Recently characterized prokaryotic Argonaute proteins (pAgos) participates in host defense by DNA interference. Here, we report that the Natronobacterium gregoryi Argonaute (NgAgo) enhances gene insertions or deletions in Pasteurella multocida and Escherichia coli at efficiencies of 80-100%. Read More

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http://dx.doi.org/10.1093/nar/gkz040DOI Listing
January 2019
2 Reads
9.112 Impact Factor

Selection of self-priming molecular replicators.

Nucleic Acids Res 2019 Jan 30. Epub 2019 Jan 30.

Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea.

Self-priming amplification of oligonucleotides is possible based on foldback of 3' ends, self-priming, and concatemerization, especially in the presence of phosphorothioate linkages. Such a simple replicative mechanism may have led to the accumulation of specific replicators at or near the origin of life. To determine how early replicators may have competed with one another, we have carried out selections with phosphorothiolated hairpins appended to a short random sequence library (N10). Read More

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http://dx.doi.org/10.1093/nar/gkz044DOI Listing
January 2019
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Plant organellar DNA polymerases repair double-stranded breaks by microhomology-mediated end-joining.

Nucleic Acids Res 2019 Jan 30. Epub 2019 Jan 30.

Laboratorio Nacional de Genómica para la Biodiversidad, Centro de Investigación y de Estudios Avanzados del IPN, Apartado Postal 629, Irapuato, Guanajuato, CP 36821, México.

Double-stranded breaks (DSBs) in plant organelles are repaired via genomic rearrangements characterized by microhomologous repeats. These microhomologous signatures predict the existence of an unidentified enzymatic machinery capable of repairing of DSBs via microhomology-mediated end-joining (MMEJ) in plant organelles. Here, we show that organellar DNA polymerases from Arabidopsis thaliana (AtPolIA and AtPolIB) perform MMEJ using microhomologous sequences as short as six nucleotides. Read More

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http://dx.doi.org/10.1093/nar/gkz039DOI Listing
January 2019
1 Read