A protein-protein interaction underlies the molecular basis for substrate recognition by an adenosine-to-inosine RNA-editing enzyme.

Abstract:

:Adenosine deaminases that act on RNA (ADARs) convert adenosine to inosine within double-stranded regions of RNA, resulting in increased transcriptomic diversity, as well as protection of cellular double-stranded RNA (dsRNA) from silencing and improper immune activation. The presence of dsRNA-binding domains (dsRBDs) in all ADARs suggests these domains are important for substrate recognition; however, the role of dsRBDs in vivo remains largely unknown. Herein, our studies indicate the Caenorhabditis elegans ADAR enzyme, ADR-2, has low affinity for dsRNA, but interacts with ADR-1, an editing-deficient member of the ADAR family, which has a 100-fold higher affinity for dsRNA. ADR-1 uses one dsRBD to physically interact with ADR-2 and a second dsRBD to bind to dsRNAs, thereby tethering ADR-2 to substrates. ADR-2 interacts with >1200 transcripts in vivo, and ADR-1 is required for 80% of these interactions. Our results identify a novel mode of substrate recognition for ADAR enzymes and indicate that protein-protein interactions can guide substrate recognition for RNA editors.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Rajendren S,Manning AC,Al-Awadi H,Yamada K,Takagi Y,Hundley HA

doi

10.1093/nar/gky800

subject

Has Abstract

pub_date

2018-10-12 00:00:00

pages

9647-9659

issue

18

eissn

0305-1048

issn

1362-4962

pii

5091960

journal_volume

46

pub_type

杂志文章
  • Dimerization specificity of all 67 B-ZIP motifs in Arabidopsis thaliana: a comparison to Homo sapiens B-ZIP motifs.

    abstract::Basic region-leucine zipper (B-ZIP) proteins are a class of dimeric sequence-specific DNA-binding proteins unique to eukaryotes. We have identified 67 B-ZIP proteins in the Arabidopsis thaliana genome. No A.thaliana B-ZIP domains are homologous with any Homo sapiens B-ZIP domains. Here, we predict the dimerization spe...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkh653

    authors: Deppmann CD,Acharya A,Rishi V,Wobbes B,Smeekens S,Taparowsky EJ,Vinson C

    更新日期:2004-06-29 00:00:00

  • InParanoid 6: eukaryotic ortholog clusters with inparalogs.

    abstract::The InParanoid eukaryotic ortholog database (http://InParanoid.sbc.su.se/) has been updated to version 6 and is now based on 35 species. We collected all available 'complete' eukaryotic proteomes and Escherichia coli, and calculated ortholog groups for all 595 species pairs using the InParanoid program. This resulted ...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkm1020

    authors: Berglund AC,Sjölund E,Ostlund G,Sonnhammer EL

    更新日期:2008-01-01 00:00:00

  • ArrayXPath: mapping and visualizing microarray gene-expression data with integrated biological pathway resources using Scalable Vector Graphics.

    abstract::Biological pathways can provide key information on the organization of biological systems. ArrayXPath (http://www.snubi.org/software/ArrayXPath/) is a web-based service for mapping and visualizing microarray gene-expression data for integrated biological pathway resources using Scalable Vector Graphics (SVG). By integ...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkh476

    authors: Chung HJ,Kim M,Park CH,Kim J,Kim JH

    更新日期:2004-07-01 00:00:00

  • Early steps of active DNA demethylation initiated by ROS1 glycosylase require three putative helix-invading residues.

    abstract::Active DNA demethylation is crucial for epigenetic control, but the underlying enzymatic mechanisms are incompletely understood. REPRESSOR OF SILENCING 1 (ROS1) is a 5-methylcytosine (5-meC) DNA glycosylase/lyase that initiates DNA demethylation in plants through a base excision repair process. The enzyme binds DNA no...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkt625

    authors: Parrilla-Doblas JT,Ponferrada-Marín MI,Roldán-Arjona T,Ariza RR

    更新日期:2013-10-01 00:00:00

  • Interferon-induced 56,000 Mr protein and its mRNA in human cells: molecular cloning and partial sequence of the cDNA.

    abstract::Treatment of responsive cells by interferons (IFNs) induces within a few hours a rise in the concentration of several proteins and mRNAs. In order to characterize these IFN-induced mRNA species, we have cloned in E. coli the cDNA made from a 17-18S poly(A)+ RNA of human fibroblastoid cells (SV80) treated with IFN-beta...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/11.5.1213

    authors: Chebath J,Merlin G,Metz R,Benech P,Revel M

    更新日期:1983-03-11 00:00:00

  • Transcription factor Sp3 antagonizes activation of the ornithine decarboxylase promoter by Sp1.

    abstract::Ornithine decarboxylase (ODC) expression is important for proliferation and is elevated in many tumor cells. We previously showed that Sp1 is a major positive regulator of ODC transcription. In this paper we have investigated transcriptional regulation of rat ODC by the closely related factor Sp3. While over-expressio...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/25.10.2012

    authors: Kumar AP,Butler AP

    更新日期:1997-05-15 00:00:00

  • RNA polymerase II stalled at a thymine dimer: footprint and effect on excision repair.

    abstract::Bulky lesions in the template strand block the progression of RNA polymerase II (RNAP II) and are repaired more rapidly than lesions in the non-transcribed strand, which do not block transcription. In order to better understand the basis of this transcription-coupled repair we developed an in vitro system with purifie...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/25.4.787

    authors: Selby CP,Drapkin R,Reinberg D,Sancar A

    更新日期:1997-02-15 00:00:00

  • Correction of the consequences of mitochondrial 3243A>G mutation in the MT-TL1 gene causing the MELAS syndrome by tRNA import into mitochondria.

    abstract::Mutations in human mitochondrial DNA are often associated with incurable human neuromuscular diseases. Among these mutations, an important number have been identified in tRNA genes, including 29 in the gene MT-TL1 coding for the tRNA(Leu(UUR)). The m.3243A>G mutation was described as the major cause of the MELAS syndr...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkr546

    authors: Karicheva OZ,Kolesnikova OA,Schirtz T,Vysokikh MY,Mager-Heckel AM,Lombès A,Boucheham A,Krasheninnikov IA,Martin RP,Entelis N,Tarassov I

    更新日期:2011-10-01 00:00:00

  • In vivo and in vitro studies of Mgs1 suggest a link between genome instability and Okazaki fragment processing.

    abstract::The non-essential MGS1 gene of Saccharomyces cerevisiae is highly conserved in eukaryotes and encodes an enzyme containing both DNA-dependent ATPase and DNA annealing activities. MGS1 appears to function in post-replicational repair processes that contribute to genome stability. In this study, we identified MGS1 as a ...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gki900

    authors: Kim JH,Kang YH,Kang HJ,Kim DH,Ryu GH,Kang MJ,Seo YS

    更新日期:2005-10-26 00:00:00

  • Subtle structural alterations in G-quadruplex DNA regulate site specificity of fluorescence light-up probes.

    abstract::G-quadruplex (G4) DNA structures are linked to key biological processes and human diseases. Small molecules that target specific G4 DNA structures and signal their presence would therefore be of great value as chemical research tools with potential to further advance towards diagnostic and therapeutic developments. Ho...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkz1205

    authors: Kumar R,Chand K,Bhowmik S,Das RN,Bhattacharjee S,Hedenström M,Chorell E

    更新日期:2020-02-20 00:00:00

  • Distribution of topoisomerase II-mediated cleavage sites and relation to structural and functional landmarks in 830 kb of Drosophila DNA.

    abstract::The pattern of sites for cleavage mediated by topoisomerase II was determined in 830 kb of cloned DNA from the Drosophila X chromosome, with the objectives of comparing it with mapped structural and functional landmarks and examining if the correlations with such landmarks reported in individual loci can be generalize...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/25.11.2041

    authors: Miassod R,Razin SV,Hancock R

    更新日期:1997-06-01 00:00:00

  • Analysis of the interaction with the hepatitis C virus mRNA reveals an alternative mode of RNA recognition by the human La protein.

    abstract::Human La protein is an essential factor in the biology of both coding and non-coding RNAs. In the nucleus, La binds primarily to 3' oligoU containing RNAs, while in the cytoplasm La interacts with an array of different mRNAs lacking a 3' UUU(OH) trailer. An example of the latter is the binding of La to the IRES domain...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkr890

    authors: Martino L,Pennell S,Kelly G,Bui TT,Kotik-Kogan O,Smerdon SJ,Drake AF,Curry S,Conte MR

    更新日期:2012-02-01 00:00:00

  • Transcription of the tRNA-tufB operon of Escherichia coli: activation, termination and antitermination.

    abstract::Signals setting the level of transcription of the tRNA-tufB operon have been studied by deletion mapping. TufB transcription was measured in vivo with plasmid-borne tRNA-tufB:galk operon fusions. Removal of the sequences from -133 to -58 with respect to the transcription start point, results in a 90% decrease of tufB ...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/15.22.9515

    authors: van Delft JH,Mariñon B,Schmidt DS,Bosch L

    更新日期:1987-11-25 00:00:00

  • The relationship of potential G-quadruplex sequences in cis-upstream regions of the human genome to SP1-binding elements.

    abstract::We have carried out a survey of potential quadruplex structure sequences (PQSS), which occur in the immediate upstream region (500 bp) of human genes. By examining the number and distribution of these we have established that there is a clear link between them and the occurrence of the SP1-binding element 'GGGCGG', su...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkn078

    authors: Todd AK,Neidle S

    更新日期:2008-05-01 00:00:00

  • Localisation of a series of intra-RNA cross-links in 16S RNA, induced by ultraviolet irradiation of Escherichia coli 30S ribosomal subunits.

    abstract::Mild ultraviolet irradiation of E. coli ribosomal subunits leads to the formation of a number of intra-RNA cross-links, in addition to the RNA-protein cross-links already reported (see refs. 9, 10). After partial ribonuclease digestion of the RNA from irradiated subunits, complexes containing these intra-RNA cross-lin...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/8.11.2397

    authors: Zwieb C,Brimacombe R

    更新日期:1980-06-11 00:00:00

  • Sequence dependent phase separation of protein-polynucleotide mixtures elucidated using molecular simulations.

    abstract::Ribonucleoprotein (RNP) granules are membraneless organelles (MLOs), which majorly consist of RNA and RNA-binding proteins and are formed via liquid-liquid phase separation (LLPS). Experimental studies investigating the drivers of LLPS have shown that intrinsically disordered proteins (IDPs) and nucleic acids like RNA...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkaa1099

    authors: Regy RM,Dignon GL,Zheng W,Kim YC,Mittal J

    更新日期:2020-12-16 00:00:00

  • Optogenetic control of Neisseria meningitidis Cas9 genome editing using an engineered, light-switchable anti-CRISPR protein.

    abstract::Optogenetic control of CRISPR-Cas9 systems has significantly improved our ability to perform genome perturbations in living cells with high precision in time and space. As new Cas orthologues with advantageous properties are rapidly being discovered and engineered, the need for straightforward strategies to control th...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkaa1198

    authors: Hoffmann MD,Mathony J,Upmeier Zu Belzen J,Harteveld Z,Aschenbrenner S,Stengl C,Grimm D,Correia BE,Eils R,Niopek D

    更新日期:2020-12-16 00:00:00

  • The nucleotide sequence at the 3'-end of Neurospora crassa 25S-rRNA and the location of a 5.8S-rRNA binding site.

    abstract::The sequence of 110 nucleotides adjacent to the 3'-end of Neurospora crassa 25S-rRNA has been derived by chemical sequencing methods. Sequences present between 40 and 85 nucleotides of the 3'-end were found to complement sequences at the 3'- and 5'-ends of 5.8S-rRNA. Interaction was shown to occur between 5.8S-rRNA an...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/9.5.1111

    authors: Kelly JM,Cox RA

    更新日期:1981-03-11 00:00:00

  • Mutational analysis of the tobacco mosaic virus 5'-leader for altered ability to enhance translation.

    abstract::Mutational analysis of the 5'-untranslated leader sequence (omega) of tobacco mosaic virus (TMV) was carried out to determine those sequences necessary for the translational enhancement associated with omega. Five deletion mutants, a single base substitution, and a 25 base replacement mutant were tested for alteration...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/16.3.883

    authors: Gallie DR,Sleat DE,Watts JW,Turner PC,Wilson TM

    更新日期:1988-02-11 00:00:00

  • iProClass: an integrated database of protein family, function and structure information.

    abstract::The iProClass database provides comprehensive, value-added descriptions of proteins and serves as a framework for data integration in a distributed networking environment. The protein information in iProClass includes family relationships as well as structural and functional classifications and features. The current v...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkg044

    authors: Huang H,Barker WC,Chen Y,Wu CH

    更新日期:2003-01-01 00:00:00

  • RB signaling prevents replication-dependent DNA double-strand breaks following genotoxic insult.

    abstract::Cell cycle checkpoints induced by DNA damage play an integral role in preservation of genomic stability by allowing cells to limit the propagation of deleterious mutations. The retinoblastoma tumor suppressor (RB) is crucial for the maintenance of the DNA damage checkpoint function because it elicits cell cycle arrest...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkg919

    authors: Bosco EE,Mayhew CN,Hennigan RF,Sage J,Jacks T,Knudsen ES

    更新日期:2004-01-02 00:00:00

  • RF-Cloning.org: an online tool for the design of restriction-free cloning projects.

    abstract::Restriction-free cloning (RF-cloning) is a PCR-based technology that expands on the QuikChange™ mutagenesis process originally popularized by Stratagene in the mid-1990s, and allows the insertion of essentially any sequence into any plasmid at any location. While RF-cloning is a powerful tool for the design of custom ...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gks396

    authors: Bond SR,Naus CC

    更新日期:2012-07-01 00:00:00

  • A simple method for N-15 labelling of exocyclic amino groups in synthetic oligodeoxynucleotides.

    abstract::The use of the ammonia deprotection step to introduce (15)N labels at specific exocyclic amino positions of adenine, cytosine, guanine or 2-aminopurine of oligodeoxynucleotides is described. ...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/22.15.2982

    authors: Acedo M,Fàbrega C,Aviño A,Goodman M,Fagan P,Wemmer D,Eritja R

    更新日期:1994-08-11 00:00:00

  • Novel m4C modification in type I restriction-modification systems.

    abstract::We identify a new subgroup of Type I Restriction-Modification enzymes that modify cytosine in one DNA strand and adenine in the opposite strand for host protection. Recognition specificity has been determined for ten systems using SMRT sequencing and each recognizes a novel DNA sequence motif. Previously characterized...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkw743

    authors: Morgan RD,Luyten YA,Johnson SA,Clough EM,Clark TA,Roberts RJ

    更新日期:2016-11-02 00:00:00

  • Conserved RNA secondary structures in Picornaviridae genomes.

    abstract::The family Picornaviridae contains important pathogens including, for example, hepatitis A virus and foot-and-mouth disease virus. The genome of these viruses is a single messenger-active (+)-RNA of 7200-8500 nt. Besides coding for the viral proteins, it also contains functionally important RNA secondary structures, a...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/29.24.5079

    authors: Witwer C,Rauscher S,Hofacker IL,Stadler PF

    更新日期:2001-12-15 00:00:00

  • A simple and efficient procedure for the synthesis of 5'-aminoalkyl oligodeoxynucleotides.

    abstract::Synthetic deoxyoligonucleotides have been 5'-aminoalkylated at the end of step-wise synthesis on the polymer support. This was achieved through the activation of the 5'-hydroxyl group as its 5'-imidazolyl derivative using carbonyldiimidazole, which was subsequently displaced with hexamethylene diamine to yield the tit...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/14.20.7985

    authors: Wachter L,Jablonski JA,Ramachandran KL

    更新日期:1986-10-24 00:00:00

  • Binding site requirements and differential representation of TGF factors in nuclear ASF-1 activity.

    abstract::Activating sequence factor 1 (ASF-1) is a nuclear DNA-binding activity that is found in monocots and dicots. It interacts with several TGACG-containing elements that have been characterized from viral and T-DNA genes, the prototypes of which are the as-1 element of the CaMV 35S promoter and the ocs element from the oc...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/23.18.3778

    authors: Lam E,Lam YK

    更新日期:1995-09-25 00:00:00

  • The genome portal of the Department of Energy Joint Genome Institute.

    abstract::The Department of Energy (DOE) Joint Genome Institute (JGI) is a national user facility with massive-scale DNA sequencing and analysis capabilities dedicated to advancing genomics for bioenergy and environmental applications. Beyond generating tens of trillions of DNA bases annually, the Institute develops and maintai...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkr947

    authors: Grigoriev IV,Nordberg H,Shabalov I,Aerts A,Cantor M,Goodstein D,Kuo A,Minovitsky S,Nikitin R,Ohm RA,Otillar R,Poliakov A,Ratnere I,Riley R,Smirnova T,Rokhsar D,Dubchak I

    更新日期:2012-01-01 00:00:00

  • Recognition of distinct HLA-DQA1 promoter elements by a single nuclear factor containing Jun and Fos or antigenically related proteins.

    abstract::The activity of MHC class II promoters depends upon conserved regulatory signals one of which, the extended X-box, contains in its X2 subregion a sequence related to the cAMP response element, CRE and to the TPA response element, TRE. Accordingly, X2 is recognized by the AP-1 factor and by other c-Jun or c-Fos contain...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/21.8.1811

    authors: Neve Ombra M,Autiero M,DeLerma Barbaro A,Barretta R,Del Pozzo G,Guardiola J

    更新日期:1993-04-25 00:00:00

  • TIGRFAMs and Genome Properties: tools for the assignment of molecular function and biological process in prokaryotic genomes.

    abstract::TIGRFAMs is a collection of protein family definitions built to aid in high-throughput annotation of specific protein functions. Each family is based on a hidden Markov model (HMM), where both cutoff scores and membership in the seed alignment are chosen so that the HMMs can classify numerous proteins according to the...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkl1043

    authors: Selengut JD,Haft DH,Davidsen T,Ganapathy A,Gwinn-Giglio M,Nelson WC,Richter AR,White O

    更新日期:2007-01-01 00:00:00