RNA binding candidates for human ADAR3 from substrates of a gain of function mutant expressed in neuronal cells.

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 Res

journal_title

Nucleic acids research

authors

Wang Y,Chung DH,Monteleone LR,Li J,Chiang Y,Toney MD,Beal PA

doi

10.1093/nar/gkz815

subject

Has Abstract

pub_date

2019-11-18 00:00:00

pages

10801-10814

issue

20

eissn

0305-1048

issn

1362-4962

pii

5573551

journal_volume

47

pub_type

杂志文章
  • Experimental maps of DNA structure at nucleotide resolution distinguish intrinsic from protein-induced DNA deformations.

    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

    authors: Azad RN,Zafiropoulos D,Ober D,Jiang Y,Chiu TP,Sagendorf JM,Rohs R,Tullius TD

    更新日期:2018-03-16 00:00:00

  • Femtosecond near-infrared laser microirradiation reveals a crucial role for PARP signaling on factor assemblies at DNA damage sites.

    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

    authors: Saquilabon Cruz GM,Kong X,Silva BA,Khatibzadeh N,Thai R,Berns MW,Yokomori K

    更新日期:2016-02-18 00:00:00

  • Fine structure mapping of an avian tumor virus RNA by immunoelectron microscopy.

    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

    authors: Castleman H,Meredith RD,Erlanger BF

    更新日期:1980-10-10 00:00:00

  • DNA replication in Physarum polycephalum: bidirectional replication of DNA within replicons.

    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

    authors: Funderud S,Andreassen R,Haugli F

    更新日期:1978-03-01 00:00:00

  • Changes in methylation pattern of albumin and alpha-fetoprotein genes in developing rat liver and neoplasia.

    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

    authors: Vedel M,Gomez-Garcia M,Sala M,Sala-Trepat JM

    更新日期:1983-07-11 00:00:00

  • Target specificity of neuronal RNA-binding protein, Mel-N1: direct binding to the 3' untranslated region of its own mRNA.

    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

    authors: Abe R,Yamamoto K,Sakamoto H

    更新日期:1996-06-01 00:00:00

  • Structure, stability and function of 5-chlorouracil modified A:U and G:U base pairs.

    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

    authors: Patra A,Harp J,Pallan PS,Zhao L,Abramov M,Herdewijn P,Egli M

    更新日期:2013-02-01 00:00:00

  • Nucleotide sequence analysis of precursor 5S RNA from Bacillus licheniformis.

    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

    authors: Stiekema WJ,de Leede-Twente R,Raué HA,Planta RJ

    更新日期:1980-10-10 00:00:00

  • Interaction of the resolving enzyme YDC2 with the four-way DNA junction.

    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

    authors: White MF,Lilley DM

    更新日期:1998-12-15 00:00:00

  • Yaf9 subunit of the NuA4 and SWR1 complexes targets histone H3K27ac through its YEATS domain.

    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

    authors: Klein BJ,Ahmad S,Vann KR,Andrews FH,Mayo ZA,Bourriquen G,Bridgers JB,Zhang J,Strahl BD,Côté J,Kutateladze TG

    更新日期:2018-01-09 00:00:00

  • NRPSpredictor2--a web server for predicting NRPS adenylation domain specificity.

    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

    authors: Röttig M,Medema MH,Blin K,Weber T,Rausch C,Kohlbacher O

    更新日期:2011-07-01 00:00:00

  • X-inactivation: quantitative predictions of protein interactions in the Xist network.

    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

    authors: Agostini F,Cirillo D,Bolognesi B,Tartaglia GG

    更新日期:2013-01-07 00:00:00

  • Meiotic recombination protein Rec12: functional conservation, crossover homeostasis and early crossover/non-crossover decision.

    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

    authors: Kan F,Davidson MK,Wahls WP

    更新日期:2011-03-01 00:00:00

  • Role of PCNA-dependent stimulation of 3'-phosphodiesterase and 3'-5' exonuclease activities of human Ape2 in repair of oxidative DNA damage.

    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

    authors: Burkovics P,Hajdú I,Szukacsov V,Unk I,Haracska L

    更新日期:2009-07-01 00:00:00

  • EWASdb: epigenome-wide association study database.

    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

    authors: Liu D,Zhao L,Wang Z,Zhou X,Fan X,Li Y,Xu J,Hu S,Niu M,Song X,Li Y,Zuo L,Lei C,Zhang M,Tang G,Huang M,Zhang N,Duan L,Lv H,Zhang M,Li J,Xu L,Kong F,Feng R,Jiang Y

    更新日期:2019-01-08 00:00:00

  • 3did: a catalog of domain-based interactions of known three-dimensional structure.

    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

    authors: Mosca R,Céol A,Stein A,Olivella R,Aloy P

    更新日期:2014-01-01 00:00:00

  • G-quadruplex formation in human telomeric (TTAGGG)4 sequence with complementary strand in close vicinity under molecularly crowded condition.

    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

    authors: Kan ZY,Lin Y,Wang F,Zhuang XY,Zhao Y,Pang DW,Hao YH,Tan Z

    更新日期:2007-01-01 00:00:00

  • Tetrahymena Genome Database (TGD): a new genomic resource for Tetrahymena thermophila research.

    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

    authors: Stover NA,Krieger CJ,Binkley G,Dong Q,Fisk DG,Nash R,Sethuraman A,Weng S,Cherry JM

    更新日期:2006-01-01 00:00:00

  • Transactivation and growth suppression by the gut-enriched Krüppel-like factor (Krüppel-like factor 4) are dependent on acidic amino acid residues and protein-protein interaction.

    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

    authors: Geiman DE,Ton-That H,Johnson JM,Yang VW

    更新日期:2000-03-01 00:00:00

  • RNIE: genome-wide prediction of bacterial intrinsic terminators.

    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

    authors: Gardner PP,Barquist L,Bateman A,Nawrocki EP,Weinberg Z

    更新日期:2011-08-01 00:00:00

  • Structural basis for RNA-genome recognition during bacteriophage Qβ replication.

    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

    authors: Gytz H,Mohr D,Seweryn P,Yoshimura Y,Kutlubaeva Z,Dolman F,Chelchessa B,Chetverin AB,Mulder FA,Brodersen DE,Knudsen CR

    更新日期:2015-12-15 00:00:00

  • Characterization of multiple alternative RNAs resulting from antisense transcription of the PR264/SC35 splicing factor gene.

    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

    authors: Sureau A,Soret J,Guyon C,Gaillard C,Dumon S,Keller M,Crisanti P,Perbal B

    更新日期:1997-11-15 00:00:00

  • Properties of a small transcribed poly A sequence in heterogeneous nuclear RNA of HeLa cells.

    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

    authors: Venkatesan S,Nakazato H,Kopp DW,Edmonds M

    更新日期:1979-03-01 00:00:00

  • Next-generation insights into regulatory T cells: expression profiling and FoxP3 occupancy in Human.

    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

    authors: Birzele F,Fauti T,Stahl H,Lenter MC,Simon E,Knebel D,Weith A,Hildebrandt T,Mennerich D

    更新日期:2011-10-01 00:00:00

  • Coordination logic of the sensing machinery in the transcriptional regulatory network of Escherichia coli.

    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

    authors: Janga SC,Salgado H,Martínez-Antonio A,Collado-Vides J

    更新日期:2007-01-01 00:00:00

  • EpoDB: a prototype database for the analysis of genes expressed during vertebrate erythropoiesis.

    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

    authors: Stoeckert CJ Jr,Salas F,Brunk B,Overton GC

    更新日期:1999-01-01 00:00:00

  • The NCBI Taxonomy database.

    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

    authors: Federhen S

    更新日期:2012-01-01 00:00:00

  • Genotyping single nucleotide polymorphisms directly from genomic DNA by invasive cleavage reaction on microspheres.

    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

    authors: Rao KV,Stevens PW,Hall JG,Lyamichev V,Neri BP,Kelso DM

    更新日期:2003-06-01 00:00:00

  • Distribution of DNA-condensing protein complexes in the adenovirus core.

    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

    authors: Pérez-Berná AJ,Marion S,Chichón FJ,Fernández JJ,Winkler DC,Carrascosa JL,Steven AC,Šiber A,San Martín C

    更新日期:2015-04-30 00:00:00

  • In vitro selection of hammerhead ribozymes containing a bulged nucleotide in stem II.

    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

    authors: Thomson JB,Sigurdsson ST,Zeuch A,Eckstein F

    更新日期:1996-11-15 00:00:00