Nucleic Acids Research

https://academic.oup.com/nar

List of Papers (Total 4,932)

Affinity maturation of a portable Fab–RNA module for chaperone-assisted RNA crystallography

Antibody fragments such as Fabs possess properties that can enhance protein and RNA crystallization and therefore can facilitate macromolecular structure determination. In particular, Fab BL3–6 binds to an AAACA RNA pentaloop closed by a GC pair with ∼100 nM affinity. The Fab and hairpin have served as a portable module for RNA crystallization. The potential for general...

The hepatitis C viral nonstructural protein 5A stabilizes growth-regulatory human transcripts

Numerous mammalian proto-oncogene and other growth-regulatory transcripts are upregulated in malignancy due to abnormal mRNA stabilization. In hepatoma cells expressing a hepatitis C virus (HCV) subgenomic replicon, we found that the viral nonstructural protein 5A (NS5A), a protein known to bind to viral RNA, also bound specifically to human cellular transcripts that encode...

A novel family of tyrosine integrases encoded by the temperate pleolipovirus SNJ2

Genomes of halophilic archaea typically contain multiple loci of integrated mobile genetic elements (MGEs). Despite the abundance of these elements, however, mechanisms underlying their site-specific integration and excision have not been investigated. Here, we identified and characterized a novel recombination system encoded by the temperate pleolipovirus SNJ2, which infects...

RAD51 and RTEL1 compensate telomere loss in the absence of telomerase

Replicative erosion of telomeres is naturally compensated by telomerase and studies in yeast and vertebrates show that homologous recombination can compensate for the absence of telomerase. We show that RAD51 protein, which catalyzes the key strand-invasion step of homologous recombination, is localized at Arabidopsis telomeres in absence of telomerase. Blocking the strand...

Characterization of DNA ADP-ribosyltransferase activities of PARP2 and PARP3: new insights into DNA ADP-ribosylation

Poly(ADP-ribose) polymerases (PARPs) act as DNA break sensors and catalyze the synthesis of polymers of ADP-ribose (PAR) covalently attached to acceptor proteins at DNA damage sites. It has been demonstrated that both mammalian PARP1 and PARP2 PARylate double-strand break termini in DNA oligonucleotide duplexes in vitro. Here, we show that mammalian PARP2 and PARP3 can PARylate...

Protein-mediated looping of DNA under tension requires supercoiling

Protein-mediated DNA looping is ubiquitous in chromatin organization and gene regulation, but to what extent supercoiling or nucleoid associated proteins promote looping is poorly understood. Using the lac repressor (LacI), a paradigmatic loop-mediating protein, we measured LacI-induced looping as a function of either supercoiling or the concentration of the HU protein, an...

WOX11 recruits a histone H3K27me3 demethylase to promote gene expression during shoot development in rice

WUSCHEL-related homeobox (WOX) genes are key regulators of meristem activity and plant development, the chromatin mechanism of which to reprogram gene expression remains unclear. Histone H3K27me3 is a chromatin mark of developmentally repressed genes. How the repressive mark is removed from specific genes during plant development is largely unknown. Here, we show that WOX11...

Brain-specific deletion of histone variant H2A.z results in cortical neurogenesis defects and neurodevelopmental disorder

Defects in neurogenesis alter brain circuit formations and may lead to neurodevelopmental disorders such as autism and schizophrenia. Histone H2A.z, a variant of histone H2A, plays critical roles in chromatin structure and epigenetic regulation, but its function and mechanism in brain development remain largely unknown. Here, we find that the deletion of H2A.z results in enhanced...

Selection, periodicity and potential function for Highly Iterative Palindrome-1 (HIP1) in cyanobacterial genomes

Highly Iterated Palindrome 1 (HIP1, GCGATCGC) is hyper-abundant in most cyanobacterial genomes. In some cyanobacteria, average HIP1 abundance exceeds one motif per gene. Such high abundance suggests a significant role in cyanobacterial biology. However, 20 years of study have not revealed whether HIP1 has a function, much less what that function might be. We show that HIP1 is 15...

Epigenomics in 3D: importance of long-range spreading and specific interactions in epigenomic maintenance

Recent progresses of genome-wide chromatin conformation capture techniques have shown that the genome is segmented into hierarchically organized spatial compartments. However, whether this non-random 3D organization only reflects or indeed contributes—and how—to the regulation of genome function remain to be elucidated. The observation in many species that 3D domains correlate...

Structure and electrical properties of DNA nanotubes embedded in lipid bilayer membranes

Engineering the synthetic nanopores through lipid bilayer membrane to access the interior of a cell is a long persisting challenge in biotechnology. Here, we demonstrate the stability and dynamics of a tile-based 6-helix DNA nanotube (DNT) embedded in POPC lipid bilayer using the analysis of 0.2 μs long equilibrium MD simulation trajectories. We observe that the head groups of...

Splicing regulation by long noncoding RNAs

Massive high-throughput sequencing techniques allowed the identification of thousands of noncoding RNAs (ncRNAs) and a plethora of different mRNA processing events occurring in higher organisms. Long ncRNAs can act directly as long transcripts or can be processed into active small si/miRNAs. They can modulate mRNA cleavage, translational repression or the epigenetic landscape of...

The mechanisms of a mammalian splicing enhancer

Exonic splicing enhancer (ESE) sequences are bound by serine & arginine-rich (SR) proteins, which in turn enhance the recruitment of splicing factors. It was inferred from measurements of splicing around twenty years ago that Drosophila doublesex ESEs are bound stably by SR proteins, and that the bound proteins interact directly but with low probability with their targets...

Riboswitching with ciprofloxacin—development and characterization of a novel RNA regulator

RNA molecules play important and diverse regulatory roles in the cell. Inspired by this natural versatility, RNA devices are increasingly important for many synthetic biology applications, e.g. optimizing engineered metabolic pathways, gene therapeutics or building up complex logical units. A major advantage of RNA is the possibility of de novo design of RNA-based sensing domains...

The C-terminal region of translesion synthesis DNA polymerase η is partially unstructured and has high conformational flexibility

Eukaryotic DNA polymerase η catalyzes translesion synthesis of thymine dimers and 8-oxoguanines. It is comprised of a polymerase domain and a C-terminal region, both of which are required for its biological function. The C-terminal region mediates interactions with proliferating cell nuclear antigen (PCNA) and other translesion synthesis proteins such as Rev1. This region...

Oxidative stress damages rRNA inside the ribosome and differentially affects the catalytic center

Intracellular levels of reactive oxygen species (ROS) increase as a consequence of oxidative stress and represent a major source of damage to biomolecules. Due to its high cellular abundance RNA is more frequently the target for oxidative damage than DNA. Nevertheless the functional consequences of damage on stable RNA are poorly understood. Using a genome-wide approach, based on...

Conserved and species-specific transcription factor co-binding patterns drive divergent gene regulation in human and mouse

The mouse is widely used as system to study human genetic mechanisms. However, extensive rewiring of transcriptional regulatory networks often confounds translation of findings between human and mouse. Site-specific gain and loss of individual transcription factor binding sites (TFBS) has caused functional divergence of orthologous regulatory loci, and so we must look beyond this...

Genome-wide dose-dependent inhibition of histone deacetylases studies reveal their roles in enhancer remodeling and suppression of oncogenic super-enhancers

Histone deacetylase inhibitors (HDACIs) are known to alter gene expression by both up- and down-regulation of protein-coding genes in normal and cancer cells. However, the exact regulatory mechanisms of action remain uncharacterized. Here we investigated genome wide dose-dependent epigenetic and transcriptome changes in response to HDACI largazole in a transformed and a non...

Two-step interrogation then recognition of DNA binding site by Integration Host Factor: an architectural DNA-bending protein

The dynamics and mechanism of how site-specific DNA-bending proteins initially interrogate potential binding sites prior to recognition have remained elusive for most systems. Here we present these dynamics for Integration Host factor (IHF), a nucleoid-associated architectural protein, using a μs-resolved T-jump approach. Our studies show two distinct DNA-bending steps during...

i-Motif of cytosine-rich human telomere DNA fragments containing natural base lesions

i-Motif (iM) is a four stranded DNA structure formed by cytosine-rich sequences, which are often present in functionally important parts of the genome such as promoters of genes and telomeres. Using electronic circular dichroism and UV absorption spectroscopies and electrophoretic methods, we examined the effect of four naturally occurring DNA base lesions on the folding and...

Structure–activity relationships and cellular mechanism of action of small molecules that enhance the delivery of oligonucleotides

The pharmacological effects of antisense and siRNA oligonucleotides are hindered by the tendency of these molecules to become entrapped in endomembrane compartments thus failing to reach their targets in the cytosol or nucleus. We have previously used high throughput screening to identify small molecules that enhance the escape of oligonucleotides from intracellular membrane...

Chemistry, mechanism and clinical status of antisense oligonucleotides and duplex RNAs

RNA plays a central role in the expression of all genes. Because any sequence within RNA can be recognized by complementary base pairing, synthetic oligonucleotides and oligonucleotide mimics offer a general strategy for controlling processes that affect disease. The two primary antisense approaches for regulating expression through recognition of cellular RNAs are single...