Nucleic Acids Research

https://academic.oup.com/nar

List of Papers (Total 5,589)

Aberrant splicing in B-cell acute lymphoblastic leukemia

Aberrant splicing is a hallmark of leukemias with mutations in splicing factor (SF)-encoding genes. Here we investigated its prevalence in pediatric B-cell acute lymphoblastic leukemias (B-ALL), where SFs are not mutated. By comparing these samples to normal pro-B cells, we found thousands of aberrant local splice variations (LSVs) per sample, with 279 LSVs in 241 genes present...

Differential analysis of chromatin accessibility and histone modifications for predicting mouse developmental enhancers

Enhancers are distal cis-regulatory elements that modulate gene expression. They are depleted of nucleosomes and enriched in specific histone modifications; thus, calling DNase-seq and histone mark ChIP-seq peaks can predict enhancers. We evaluated nine peak-calling algorithms for predicting enhancers validated by transgenic mouse assays. DNase and H3K27ac peaks were consistently...

Shared nucleotide flanks confer transcriptional competency to bZip core motifs

Sequence-specific DNA binding recruits transcription factors (TFs) to the genome to regulate gene expression. Here, we perform high resolution mapping of CEBP proteins to determine how sequence dictates genomic occupancy. We demonstrate a fundamental difference between the sequence repertoire utilized by CEBPs in vivo versus the palindromic sequence preference reported by...

Efficient CRISPR/Cas9-mediated editing of trinucleotide repeat expansion in myotonic dystrophy patient-derived iPS and myogenic cells

CRISPR/Cas9 is an attractive platform to potentially correct dominant genetic diseases by gene editing with unprecedented precision. In the current proof-of-principle study, we explored the use of CRISPR/Cas9 for gene-editing in myotonic dystrophy type-1 (DM1), an autosomal-dominant muscle disorder, by excising the CTG-repeat expansion in the 3′-untranslated-region (UTR) of the...

Bidirectional regulation of adenosine-to-inosine (A-to-I) RNA editing by DEAH box helicase 9 (DHX9) in cancer

Adenosine-to-inosine (A-to-I) RNA editing entails the enzymatic deamination of adenosines to inosines by adenosine deaminases acting on RNA (ADARs). Dysregulated A-to-I editing has been implicated in various diseases, including cancers. However, the precise factors governing the A-to-I editing and their physiopathological implications remain as a long-standing question. Herein...

Single molecule tracking reveals that the bacterial SMC complex moves slowly relative to the diffusion of the chromosome

Structural Maintenance of Chromosomes (SMC) proteins and their complex partners (ScpA and ScpB in many bacteria) are involved in chromosome compaction and segregation in all kinds of organisms. We employed single molecule tracking (SMT), tracking of chromosomal loci, and single molecule counting in Bacillus subtilis to show that in slow growing cells, ∼30 Smc dimers move...

Cyclic di-GMP integrates functionally divergent transcription factors into a regulation pathway for antioxidant defense

Cyclic diguanylate monophosphate (c-di-GMP) is a global signaling molecule that modulates diverse cellular processes through its downstream receptors. However, no study has fully clarified the mechanisms by which c-di-GMP organizes functionally divergent regulators to drive the gene expression for coping with environmental stress. Here, we reported that c-di-GMP can integrate two...

High-resolution RNA 3′-ends mapping of bacterial Rho-dependent transcripts

Transcription termination in bacteria can occur either via Rho-dependent or independent (intrinsic) mechanisms. Intrinsic terminators are composed of a stem-loop RNA structure followed by a uridine stretch and are known to terminate in a precise manner. In contrast, Rho-dependent terminators have more loosely defined characteristics and are thought to terminate in a diffuse...

RecBCD coordinates repair of two ends at a DNA double-strand break, preventing aberrant chromosome amplification

DNA double-strand break (DSB) repair is critical for cell survival. A diverse range of organisms from bacteria to humans rely on homologous recombination for accurate DSB repair. This requires both coordinate action of the two ends of a DSB and stringent control of the resultant DNA replication to prevent unwarranted DNA amplification and aneuploidy. In Escherichia coli, RecBCD...

Transfer-matrix calculations of the effects of tension and torque constraints on DNA–protein interactions

Organization and maintenance of the chromosomal DNA in living cells strongly depends on the DNA interactions with a plethora of DNA-binding proteins. Single-molecule studies show that formation of nucleoprotein complexes on DNA by such proteins is frequently subject to force and torque constraints applied to the DNA. Although the existing experimental techniques allow to exert...

5-Formylcytosine mediated DNA–protein cross-links block DNA replication and induce mutations in human cells

5-Formylcytosine (5fC) is an epigenetic DNA modification introduced via TET protein-mediated oxidation of 5-methyl-dC. We recently reported that 5fC form reversible DNA–protein conjugates (DPCs) with histone proteins in living cells (Ji et al. (2017) Angew. Chem. Int. Ed., 56:14130–14134). We now examined the effects of 5fC mediated DPCs on DNA replication. Synthetic DNA duplexes...

HITS-CLIP in various brain areas reveals new targets and new modalities of RNA binding by fragile X mental retardation protein

Fragile X syndrome (FXS), the most common form of inherited intellectual disability, is due to the functional deficiency of the fragile X mental retardation protein (FMRP), an RNA-binding protein involved in translational regulation of many messenger RNAs, playing key roles in synaptic morphology and plasticity. To date, no effective treatment for FXS is available. We searched...

Control of mRNA decapping by autoinhibition

5′ mediated cytoplasmic RNA decay is a conserved cellular process in eukaryotes. While the functions of the structured core domains in this pathway are well-studied, the role of abundant intrinsically disordered regions (IDRs) is lacking. Here we reconstitute the Dcp1:Dcp2 complex containing a portion of the disordered C-terminus and show its activity is autoinhibited by linear...

Bacterial EndoMS/NucS acts as a clamp-mediated mismatch endonuclease to prevent asymmetric accumulation of replication errors

Mismatch repair (MMR) systems based on MutS eliminate mismatches originating from replication errors. Despite extensive conservation of mutS homologues throughout the three domains of life, Actinobacteria and some archaea do not have genes homologous to mutS. Here, we report that EndoMS/NucS of Corynebacterium glutamicum is the mismatch-specific endonuclease that functions...

Properties of gene expression and chromatin structure with mechanically regulated elongation

In recent years, physical elements of transcription have emerged as central in our understanding of gene expression. Recent work has been done introducing a simple description of the basic physical elements of transcription where RNA elongation, RNA polymerase (RNAP) rotation and DNA supercoiling are coupled (1). Here we generalize this framework to accommodate the behavior of...

gRINN: a tool for calculation of residue interaction energies and protein energy network analysis of molecular dynamics simulations

Atomistic molecular dynamics (MD) simulations generate a wealth of information related to the dynamics of proteins. If properly analyzed, this information can lead to new insights regarding protein function and assist wet-lab experiments. Aiming to identify interactions between individual amino acid residues and the role played by each in the context of MD simulations, we present...

VarAFT: a variant annotation and filtration system for human next generation sequencing data

With the rapidly developing high-throughput sequencing technologies known as next generation sequencing or NGS, our approach to gene hunting and diagnosis has drastically changed. In <10 years, these technologies have moved from gene panel to whole genome sequencing and from an exclusively research context to clinical practice. Today, the limit is not the sequencing of one, many...

The Galaxy platform for accessible, reproducible and collaborative biomedical analyses: 2018 update

Galaxy (homepage: https://galaxyproject.org, main public server: https://usegalaxy.org) is a web-based scientific analysis platform used by tens of thousands of scientists across the world to analyze large biomedical datasets such as those found in genomics, proteomics, metabolomics and imaging. Started in 2005, Galaxy continues to focus on three key challenges of data-driven...

PaintOmics 3: a web resource for the pathway analysis and visualization of multi-omics data

The increasing availability of multi-omic platforms poses new challenges to data analysis. Joint visualization of multi-omics data is instrumental in better understanding interconnections across molecular layers and in fully utilizing the multi-omic resources available to make biological discoveries. We present here PaintOmics 3, a web-based resource for the integrated...

MetExplore: collaborative edition and exploration of metabolic networks

Metabolism of an organism is composed of hundreds to thousands of interconnected biochemical reactions responding to environmental or genetic constraints. This metabolic network provides a rich knowledge to contextualize omics data and to elaborate hypotheses on metabolic modulations. Nevertheless, performing this kind of integrative analysis is challenging for end users with not...

oriTfinder: a web-based tool for the identification of origin of transfers in DNA sequences of bacterial mobile genetic elements

oriTfinder is a web server that facilitates the rapid identification of the origin of transfer site (oriT) of a conjugative plasmid or chromosome-borne integrative and conjugative element. The utilized back-end database oriTDB was built upon more than one thousand known oriT regions of bacterial mobile genetic elements (MGEs) as well as the known MGE-encoding relaxases and type...

HMMER web server: 2018 update

The HMMER webserver [http://www.ebi.ac.uk/Tools/hmmer] is a free-to-use service which provides fast searches against widely used sequence databases and profile hidden Markov model (HMM) libraries using the HMMER software suite (http://hmmer.org). The results of a sequence search may be summarized in a number of ways, allowing users to view and filter the significant hits by...

CoNekT: an open-source framework for comparative genomic and transcriptomic network analyses

The recent accumulation of gene expression data in the form of RNA sequencing creates unprecedented opportunities to study gene regulation and function. Furthermore, comparative analysis of the expression data from multiple species can elucidate which functional gene modules are conserved across species, allowing the study of the evolution of these modules. However, performing...

Kinact: a computational approach for predicting activating missense mutations in protein kinases

Protein phosphorylation is tightly regulated due to its vital role in many cellular processes. While gain of function mutations leading to constitutive activation of protein kinases are known to be driver events of many cancers, the identification of these mutations has proven challenging. Here we present Kinact, a novel machine learning approach for predicting kinase activating...