Abstract:
:Human ADAR3 is a catalytically inactive member of the Adenosine Deaminase Acting on RNA (ADAR) protein family, whose active members catalyze A-to-I RNA editing in metazoans. Until now, the reasons for the catalytic incapability of ADAR3 has not been defined and its biological function rarely explored. Yet, its exclusive expression in the brain and involvement in learning and memory suggest a central role in the nervous system. Here we describe the engineering of a catalytically active ADAR3 enzyme using a combination of computational design and functional screening. Five mutations (A389V, V485I, E527Q, Q549R and Q733D) engender RNA deaminase in human ADAR3. By way of its catalytic activity, the ADAR3 pentamutant was used to identify potential binding targets for wild type ADAR3 in a human glioblastoma cell line. Novel ADAR3 binding sites discovered in this manner include the 3'-UTRs of the mRNAs encoding early growth response 1 (EGR1) and dual specificity phosphatase 1 (DUSP1); both known to be activity-dependent immediate early genes that respond to stimuli in the brain. Further studies reveal that the wild type ADAR3 protein can regulate transcript levels for DUSP1 and EGR1, suggesting a novel role ADAR3 may play in brain function.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Wang Y,Chung DH,Monteleone LR,Li J,Chiang Y,Toney MD,Beal PAdoi
10.1093/nar/gkz815subject
Has Abstractpub_date
2019-11-18 00:00:00pages
10801-10814issue
20eissn
0305-1048issn
1362-4962pii
5573551journal_volume
47pub_type
杂志文章abstract::Recognition of DNA by proteins depends on DNA sequence and structure. Often unanswered is whether the structure of naked DNA persists in a protein-DNA complex, or whether protein binding changes DNA shape. While X-ray structures of protein-DNA complexes are numerous, the structure of naked cognate DNA is seldom availa...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gky033
更新日期:2018-03-16 00:00:00
abstract::Laser microirradiation is a powerful tool for real-time single-cell analysis of the DNA damage response (DDR). It is often found, however, that factor recruitment or modification profiles vary depending on the laser system employed. This is likely due to an incomplete understanding of how laser conditions/dosages affe...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkv976
更新日期:2016-02-18 00:00:00
abstract::The RNA of a deleted strain (lacking Src gene) of an avian sarcoma virus (ASV) was examined by a newly developed immunoelectron microscopic procedure which uses anti-nucleotide antibodies as probes. After denaturation of the RNA and reaction with a high affinity, highly specific anti-7-methylguanosine-5'-phosphate (an...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/8.19.4485
更新日期:1980-10-10 00:00:00
abstract::The direction of replication of DNA within replicons of Physarum polycephalum was studied by pulse-labelling with 5-bromouracil-deoxyriboside (BrdUrd) and 3H-adenosine deoxyriboside (dAdo), followed by ultraviolet- (UV) -photolysis and analysis of molecular weights of single strand DNA fragments on alkaline sucrose gr...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/5.3.713
更新日期:1978-03-01 00:00:00
abstract::To determine whether methylation changes in specific DNA sequences of the albumin and AFP genes are implicated in the modulation of transcriptional activity during rat liver development and neoplasia we have analysed the methylation pattern of C-C-G-G sequences within these genes in DNA isolated from fetal and adult h...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/11.13.4335
更新日期:1983-07-11 00:00:00
abstract::We have identified cDNAs encoding Mel-N1, the mouse homologue of a human nervous system-specific RNA-binding protein, Hel-N1. Two major mRNA transcripts of Mel-N1 were detected predominantly in the adult mouse brain by Northern blot analysis. To gain insight into the RNA binding specificity of Mel-N1, we performed ite...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/24.11.2011
更新日期:1996-06-01 00:00:00
abstract::The thymine analog 5-chlorouridine, first reported in the 1950s as anti-tumor agent, is known as an effective mutagen, clastogen and toxicant as well as an effective inducer of sister-chromatid exchange. Recently, the first microorganism with a chemically different genome was reported; the selected Escherichia coli st...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gks1316
更新日期:2013-02-01 00:00:00
abstract::The complete nucleotide sequences of the various precursor 5S RNA species occurring in Bacillus licheniformis have been elucidated. The B. licheniformis precursors contain a 5'-precursor-specific segment of 95 nucleotides which is four times as long as the corresponding segment of the p5S RNAs from the closely related...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/8.19.4535
更新日期:1980-10-10 00:00:00
abstract::Holliday junctions (four-way DNA junctions), formed during homologous recombination, are bound and resolved by junction-specific endonucleases to yield recombinant duplex DNA products. The junction-resolving enzymes are a structurally diverse class of proteins that nevertheless have many properties in common; in parti...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/26.24.5609
更新日期:1998-12-15 00:00:00
abstract::Yaf9 is an integral part of the NuA4 acetyltransferase and the SWR1 chromatin remodeling complexes. Here, we show that Yaf9 associates with acetylated histone H3 with high preference for H3K27ac. The crystal structure of the Yaf9 YEATS domain bound to the H3K27ac peptide reveals that the sequence C-terminal to K27ac s...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkx1151
更新日期:2018-01-09 00:00:00
abstract::The products of many bacterial non-ribosomal peptide synthetases (NRPS) are highly important secondary metabolites, including vancomycin and other antibiotics. The ability to predict substrate specificity of newly detected NRPS Adenylation (A-) domains by genome sequencing efforts is of great importance to identify an...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkr323
更新日期:2011-07-01 00:00:00
abstract::The transcriptional silencing of one of the female X-chromosomes is a finely regulated process that requires accumulation in cis of the long non-coding RNA X-inactive-specific transcript (Xist) followed by a series of epigenetic modifications. Little is known about the molecular machinery regulating initiation and mai...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gks968
更新日期:2013-01-07 00:00:00
abstract::In fission yeast and other eukaryotes, Rec12 (Spo11) is thought to catalyze the formation of dsDNA breaks (DSBs) that initiate homologous recombination in meiosis. Rec12 is orthologous to the catalytic subunit of topoisomerase VI (Top6A). Guided by the crystal structure of Top6A, we engineered the rec12 locus to encod...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkq993
更新日期:2011-03-01 00:00:00
abstract::Human Ape2 protein has 3' phosphodiesterase activity for processing 3'-damaged DNA termini, 3'-5' exonuclease activity that supports removal of mismatched nucleotides from the 3'-end of DNA, and a somewhat weak AP-endonuclease activity. However, very little is known about the role of Ape2 in DNA repair processes. Here...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkp357
更新日期:2009-07-01 00:00:00
abstract::DNA methylation, the most intensively studied epigenetic modification, plays an important role in understanding the molecular basis of diseases. Furthermore, epigenome-wide association study (EWAS) provides a systematic approach to identify epigenetic variants underlying common diseases/phenotypes. However, there is n...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gky942
更新日期:2019-01-08 00:00:00
abstract::The database of 3D interacting domains (3did, available online for browsing and bulk download at http://3did.irbbarcelona.org) is a catalog of protein-protein interactions for which a high-resolution 3D structure is known. 3did collects and classifies all structural templates of domain-domain interactions in the Prote...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkt887
更新日期:2014-01-01 00:00:00
abstract::Chromosomes in vertebrates are protected at both ends by telomere DNA composed of tandem (TTAGGG)n repeats. DNA replication produces a blunt-ended leading strand telomere and a lagging strand telomere carrying a single-stranded G-rich overhang at its end. The G-rich strand can form G-quadruplex structure in the presen...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkm203
更新日期:2007-01-01 00:00:00
abstract::We have developed a web-based resource (available at www.ciliate.org) for researchers studying the model ciliate organism Tetrahymena thermophila. Employing the underlying database structure and programming of the Saccharomyces Genome Database, the Tetrahymena Genome Database (TGD) integrates the wealth of knowledge g...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkj054
更新日期:2006-01-01 00:00:00
abstract::Gut-enriched Krüppel-like factor (GKLF or KLF4) is a pleiotropic (activating and repressive) transcription factor. This study characterizes the mechanisms of transactivation by GKLF. Using a GAL4 fusion assay, the activating domain of murine GKLF was localized to the 109 amino acid residues in the N-terminus. Site-dir...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/28.5.1106
更新日期:2000-03-01 00:00:00
abstract::Bacterial Rho-independent terminators (RITs) are important genomic landmarks involved in gene regulation and terminating gene expression. In this investigation we present RNIE, a probabilistic approach for predicting RITs. The method is based upon covariance models which have been known for many years to be the most a...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkr168
更新日期:2011-08-01 00:00:00
abstract::Upon infection of Escherichia coli by bacteriophage Qβ, the virus-encoded β-subunit recruits host translation elongation factors EF-Tu and EF-Ts and ribosomal protein S1 to form the Qβ replicase holoenzyme complex, which is responsible for amplifying the Qβ (+)-RNA genome. Here, we use X-ray crystallography, NMR spect...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkv1212
更新日期:2015-12-15 00:00:00
abstract::The PR264/SC35 splicing factor belongs to the family of SR proteins which function as essential and alternative splicing factors. Here, we report that the human PR264/SC35 locus is bidirectionally transcribed. Double in situ hybridization experiments have allowed simultaneous detection of sense and antisense RNA in hu...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/25.22.4513
更新日期:1997-11-15 00:00:00
abstract::A class of heterogeneous nuclear RNA (hnRNA) molecules contain an internal transcribed poly A sequence of close to 25 uninterrupted AMP residues. HnRNA molecules containing this sequence are separable from those containing the large 3' terminal poly A sequence on the basis of their differential affinity for oligo dT c...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/6.3.1097
更新日期:1979-03-01 00:00:00
abstract::Regulatory T-cells (Treg) play an essential role in the negative regulation of immune answers by developing an attenuated cytokine response that allows suppressing proliferation and effector function of T-cells (CD4(+) Th). The transcription factor FoxP3 is responsible for the regulation of many genes involved in the ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkr444
更新日期:2011-10-01 00:00:00
abstract::The active and inactive state of transcription factors in growing cells is usually directed by allosteric physicochemical signals or metabolites, which are in turn either produced in the cell or obtained from the environment by the activity of the products of effector genes. To understand the regulatory dynamics and t...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkm743
更新日期:2007-01-01 00:00:00
abstract::EpoDB is a database of genes expressed in vertebrate red blood cells. It is also a prototype for the creation of cell and tissue-specific databases from multiple external sources. The information in EpoDB obtained from GenBank, SWISS-PROT, Transfac, TRRD and GERD is curated to provide high quality data for sequence an...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/27.1.200
更新日期:1999-01-01 00:00:00
abstract::The NCBI Taxonomy database (http://www.ncbi.nlm.nih.gov/taxonomy) is the standard nomenclature and classification repository for the International Nucleotide Sequence Database Collaboration (INSDC), comprising the GenBank, ENA (EMBL) and DDBJ databases. It includes organism names and taxonomic lineages for each of the...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkr1178
更新日期:2012-01-01 00:00:00
abstract::Here we report proof-of-principle for a microsphere-based genotyping assay that detects single nucleotide polymorphisms (SNPs) directly from human genomic DNA samples. This assay is based on a structure-specific cleavage reaction that achieves single base discrimination with a 5'-nuclease which recognizes a tripartite...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gng066
更新日期:2003-06-01 00:00:00
abstract::Genome packing in adenovirus has long evaded precise description, since the viral dsDNA molecule condensed by proteins (core) lacks icosahedral order characteristic of the virus protein coating (capsid). We show that useful insights regarding the organization of the core can be inferred from the analysis of spatial di...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkv187
更新日期:2015-04-30 00:00:00
abstract::Hammerhead ribozymes were transcribed from a dsDNA template containing four random nucleotides between stems II and III, which replace the naturally occurring GAA nucleotides. In vitro selection was used to select hammerhead ribozymes capable of in cis cleavage using denaturing polyacrylamide gels for the isolation of...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/24.22.4401
更新日期:1996-11-15 00:00:00