Nucleic Acids Research

https://academic.oup.com/nar

List of Papers (Total 3,942)

DNA Data Bank of Japan: 30th anniversary

The DNA Data Bank of Japan (DDBJ) Center (http://www.ddbj.nig.ac.jp) has been providing public data services for 30 years since 1987. We are collecting nucleotide sequence data and associated biological information from researchers as a member of the International Nucleotide Sequence Database Collaboration (INSDC), in collaboration with the US National Center for Biotechnology...

Design and implementation of a synthetic pre-miR switch for controlling miRNA biogenesis in mammals

Synthetic RNA-based systems have increasingly been used for the regulation of eukaryotic gene expression. Due to their structural properties, riboregulators provide a convenient basis for the development of ligand-dependent controllable systems. Here, we demonstrate reversible conditional control of miRNA biogenesis with an aptamer domain as a sensing unit connected to a natural...

Arrayed mutant haploid embryonic stem cell libraries facilitate phenotype-driven genetic screens

Forward genetic screens using mammalian embryonic stem (ES) cells have identified genes required for numerous cellular processes. However, loss-of-function screens are more difficult to conduct in diploid cells because, in most cases, both alleles of a gene must be mutated to exhibit a phenotype. Recently, mammalian haploid ES cell lines were successfully established and applied...

Multiple RNA structures affect translation initiation and UGA redefinition efficiency during synthesis of selenoprotein P

Gene-specific expansion of the genetic code allows for UGA codons to specify the amino acid selenocysteine (Sec). A striking example of UGA redefinition occurs during translation of the mRNA coding for the selenium transport protein, selenoprotein P (SELENOP), which in vertebrates may contain up to 22 in-frame UGA codons. Sec incorporation at the first and downstream UGA codons...

Structural basis for the GTP specificity of the RNA kinase domain of fungal tRNA ligase

Fungal tRNA ligase (Trl1) is an essential enzyme that repairs RNA breaks with 2′,3′-cyclic-PO4 and 5′-OH ends inflicted during tRNA splicing and non-canonical mRNA splicing in the fungal unfolded protein response. Trl1 is composed of C-terminal cyclic phosphodiesterase and central polynucleotide kinase domains that heal the broken ends to generate the 3′-OH,2′-PO4 and 5′-PO4...

PARP1 changes from three-dimensional DNA damage searching to one-dimensional diffusion after auto-PARylation or in the presence of APE1

PARP1-dependent poly-ADP-ribosylation (PARylation) participates in the repair of many forms of DNA damage. Here, we used atomic force microscopy (AFM) and single molecule fluorescence microscopy to examine the interactions of PARP1 with common DNA repair intermediates. AFM volume analysis indicates that PARP1 binds to DNA at nicks, abasic (AP) sites, and ends as a monomer. Single...

Characteristic arrangement of nucleosomes is predictive of chromatin interactions at kilobase resolution

High-throughput chromosome conformation capture (3C) technologies, such as Hi-C, have made it possible to survey 3D genome structure. However, obtaining 3D profiles at kilobase resolution at low cost remains a major challenge. Therefore, we herein present an algorithm for precise identification of chromatin interaction sites at kilobase resolution from MNase-seq data, termed...

Global inhibition of transcription causes an increase in histone H2A.Z incorporation within gene bodies

H2A.Z histone variant is an important regulator of gene transcription, which is enriched at regulatory regions but is also found within gene bodies. Recent evidence suggests that active recruitment of H2A.Z within gene bodies is required to induce gene repression. In contrast to this view, we show that global inhibition of transcription results in H2A.Z accumulation at gene...

Meta-analysis of DNA double-strand break response kinetics

Most proteins involved in the DNA double-strand break response (DSBR) accumulate at the damage sites, where they perform functions related to damage signaling, chromatin remodeling and repair. Over the last two decades, studying the accumulation of many DSBR proteins provided information about their functionality and underlying mechanisms of action. However, comparison and...

Conserved non-coding elements: developmental gene regulation meets genome organization

Comparative genomics has revealed a class of non-protein-coding genomic sequences that display an extraordinary degree of conservation between two or more organisms, regularly exceeding that found within protein-coding exons. These elements, collectively referred to as conserved non-coding elements (CNEs), are non-randomly distributed across chromosomes and tend to cluster in the...

The RNA binding protein EWS is broadly involved in the regulation of pri-miRNA processing in mammalian cells

The Ewing Sarcoma protein (EWS) is a multifaceted RNA binding protein (RBP) with established roles in transcription, pre-mRNA processing and DNA damage response. By generating high quality EWS–RNA interactome, we uncovered its specific and prevalent interaction with a large subset of primary microRNAs (pri-miRNAs) in mammalian cells. Knockdown of EWS reduced, whereas...

The MRPP1/MRPP2 complex is a tRNA-maturation platform in human mitochondria

Mitochondrial polycistronic transcripts are extensively processed to give rise to functional mRNAs, rRNAs and tRNAs; starting with the release of tRNA elements through 5′-processing by RNase P (MRPP1/2/3-complex) and 3′-processing by RNase Z (ELAC2). Here, we show using in vitro experiments that MRPP1/2 is not only a component of the mitochondrial RNase P but that it retains the...