Abstract:
:Single genes are often subject to alternative splicing, which generates alternative mature mRNAs. This phenomenon is widespread in animals, and observed in over 90% of human genes. Recent data suggest it may also be common in Apicomplexa. These parasites have small genomes, and economy of DNA is evolutionarily favoured in this phylum. We investigated the mechanism of alternative splicing in Toxoplasma gondii, and have identified and localized TgSR3, a homologue of ASF/SF2 (alternative-splicing factor/splicing factor 2, a serine-arginine-rich, or SR protein) to a subnuclear compartment. In addition, we conditionally overexpressed this protein, which was deleterious to growth. qRT-PCR was used to confirm perturbation of splicing in a known alternatively-spliced gene. We performed high-throughput RNA-seq to determine the extent of splicing modulated by this protein. Current RNA-seq algorithms are poorly suited to compact parasite genomes, and hence we complemented existing tools by writing a new program, GeneGuillotine, that addresses this deficiency by segregating overlapping reads into distinct genes. In order to identify the extent of alternative splicing, we released another program, JunctionJuror, that detects changes in intron junctions. Using this program, we identified about 2000 genes that were constitutively alternatively spliced in T. gondii. Overexpressing the splice regulator TgSR3 perturbed alternative splicing in over 1000 genes.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Yeoh LM,Goodman CD,Hall NE,van Dooren GG,McFadden GI,Ralph SAdoi
10.1093/nar/gkv311subject
Has Abstractpub_date
2015-05-19 00:00:00pages
4661-75issue
9eissn
0305-1048issn
1362-4962pii
gkv311journal_volume
43pub_type
杂志文章abstract::HAP1, also known as APE/Ref-1, is the major apurinic/apyrimidinic (AP) endonuclease in human cells. Previous structural studies have suggested a possible role for the Asp-210 residue of HAP1 in the enzymatic function of this enzyme. Here, we demonstrate that substitution of Asp-210 by Asn or Ala eliminates the AP endo...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/28.11.2207
更新日期:2000-06-01 00:00:00
abstract::High-throughput sequencing technologies enable direct approaches to catalog and analyze snapshots of the total small RNA content of living cells. Characterization of high-throughput sequencing data requires bioinformatic tools offering a wide perspective of the small RNA transcriptome. Here we present SeqBuster, a hig...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkp1127
更新日期:2010-03-01 00:00:00
abstract::IL-2 gene expression in activated T-cells is initiated by chromatin remodeling at the IL-2 proximal promoter and conversion of a transcriptional repressor into a potent transcriptional activator. A purine-box regulator complex was purified from activated Jurkat T-cell nuclei based on sequence-specific DNA binding to t...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkm117
更新日期:2007-01-01 00:00:00
abstract::Eucaryotic ribosome biogenesis involves many cis-acting sequences and trans-acting factors, including snoRNAS: We have used directed mutagenesis of rDNA plasmids in yeast to identify critical sequence and structural elements within and flanking the ITS2-proximal stem. This base paired structure, present in the mature ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/29.10.2106
更新日期:2001-05-15 00:00:00
abstract::In this article, we introduce the Gypsy Database (GyDB) of mobile genetic elements, an in-progress database devoted to the non-redundant analysis and evolutionary-based classification of mobile genetic elements. In this first version, we contemplate eukaryotic Ty3/Gypsy and Retroviridae long terminal repeats (LTR) ret...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkm697
更新日期:2008-01-01 00:00:00
abstract::The DNA sequence of the spacer (plus flanking) regions separating the 16S rRNA and 23S rRNA genes of two presumptive rDNA operons of the archaebacterium Methanococcus vannielii was determined. The spacers are 156 and 242 base pairs in size and they share a sequence homology of 49 base pairs following the 3' terminus o...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/11.21.7537
更新日期:1983-11-11 00:00:00
abstract::Three-dimensional protein structures provide invaluable information for understanding and regulating biological functions of proteins. The GalaxyWEB server predicts protein structure from sequence by template-based modeling and refines loop or terminus regions by ab initio modeling. This web server is based on the met...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gks493
更新日期:2012-07-01 00:00:00
abstract::We provide a novel web service, called rQuant.web, allowing convenient access to tools for quantitative analysis of RNA sequencing data. The underlying quantitation technique rQuant is based on quadratic programming and estimates different biases induced by library preparation, sequencing and read mapping. It can tack...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkq448
更新日期:2010-07-01 00:00:00
abstract::Hybridization intensities of 30 distinct short duplex DNAs measured on spotted microarrays, were directly compared with thermodynamic stabilities measured in solution. DNA sequences were designed to promote formation of perfect match, or hybrid duplexes containing tandem mismatches. Thermodynamic parameters DeltaH deg...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkm865
更新日期:2007-01-01 00:00:00
abstract::KEYnet is a database where gene and protein names are hierarchically structured. Particular care has been devoted to the search and organisation of synonyms. The structuring is based on biological criteria in order to assist the user in the data search and to minimise the risk of loss of information. Links to the EMBL...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/27.1.365
更新日期:1999-01-01 00:00:00
abstract::We describe a rapid fluorescence indicator displacement assay (R-FID) to evaluate the affinity and the selectivity of compounds binding to different DNA structures. We validated the assay using a library of 30 well-known nucleic acid binders containing a variety chemical scaffolds. We used a combination of principal c...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gky019
更新日期:2018-04-20 00:00:00
abstract::We have developed a comprehensive resource devoted to biologists wanting to optimize the use of gene trap clones in their experiments. We have processed 300 602 such clones from both public and private projects to generate 28,199 'UniTraps', i.e. distinct collections of unambiguous insertions at the same subgenic regi...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkm825
更新日期:2008-01-01 00:00:00
abstract::The nucleotide sequence of the portion of a Bacillus subtilis (strain PAP115) 3 kb Pst I fragment which contains an endo-beta-1, 4-glucanase gene has been determined. This gene encodes a protein of 499 amino acid residues (Mr = 55,234) with a typical B. subtilis signal peptide. Escherichia coli which has been transfor...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/14.22.9159
更新日期:1986-11-25 00:00:00
abstract::Genome length complementary DNA (cDNA) transcripts were synthesized in vitro by using purified virions of a cloned isolate of mouse sarcoma virus (MSV Clone 124). The cDNA transcripts were converted to double-stranded form by utilizing DNase-digested calf thymus DNA primers and E. coli DNA polymerase I. Restriction en...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/6.5.1863
更新日期:1979-01-01 00:00:00
abstract::Conserved segments in DNA or protein sequences are strong candidates for functional elements and thus appropriate methods for computing them need to be developed and compared. We describe five methods and computer programs for finding highly conserved blocks within previously computed multiple alignments, primarily fo...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/27.19.3899
更新日期:1999-10-01 00:00:00
abstract::Thymine DNA glycosylase (TDG) is a DNA repair enzyme that excises a variety of mismatched or damaged nucleotides (nts), e.g. dU, dT, 5fC and 5caC. TDG is shown to play essential roles in maintaining genome integrity and correctly programming epigenetic modifications through DNA demethylation. After locating the lesion...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gky386
更新日期:2018-06-20 00:00:00
abstract::The SeqA protein binds hemi-methylated GATC sites and forms structures that sequester newly replicated origins and trail the replication forks. Cells that lack SeqA display signs of replication fork disintegration. The broken forks could arise because of over-initiation (the launching of too many forks) or lack of dyn...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkx263
更新日期:2017-06-20 00:00:00
abstract::To organize data resulting from the phenotypic characterization of a library of 30,000 T-DNA enhancer trap (ET) insertion lines of rice (Oryza sativa L cv. Nipponbare), we developed the Oryza Tag Line (OTL) database (http://urgi.versailles.inra.fr/OryzaTagLine/). OTL structure facilitates forward genetic search for sp...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkm762
更新日期:2008-01-01 00:00:00
abstract::The complete nucleotide sequence of the mitochondrial DNA of the amphioxus Branchiostoma lanceolatum has been determined. This mitochondrial genome is small (15 076 bp) because of the short size of the two rRNA genes and the tRNA genes. In addition, this genome contains a very short non-coding region (57 bp) with no s...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/26.13.3279
更新日期:1998-07-01 00:00:00
abstract::A method is presented for the purification of mRNAs and the identification of structural gene sequences in recombinant DNA molecules. RNA is hybridized to double-stranded linear DNA such that R-loops are formed between most DNAs and their complementary RNA sequences. These R-loops are purified from unhybridized RNAs b...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/6.7.2483
更新日期:1979-06-11 00:00:00
abstract::The purpose of this work was to analyse at the molecular level the DNA recognized by the antibodies to Z-DNA in in situ experiments. Antibodies to Z-DNA interact strongly with R-band positive heterochromatic segments of fixed metaphase chromosomes of Cebus (Viegas-Pequignot et al., 1983). These segments are constitute...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/14.8.3197
更新日期:1986-04-25 00:00:00
abstract::IHF and HU are two heterodimeric nucleoid-associated proteins (NAP) that belong to the same protein family but interact differently with the DNA. IHF is a sequence-specific DNA-binding protein that bends the DNA by over 160°. HU is the most conserved NAP, which binds non-specifically to duplex DNA with a particular pr...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkr1236
更新日期:2012-04-01 00:00:00
abstract::Signal transduction ATPases with numerous domains (STAND) get activated through inducer-dependent assembly into multimeric platforms. This switch relies on the conversion of their nucleotide-binding oligomerization domain (NOD) from a closed, ADP-bound form to an open, ATP-bound form. The NOD closed form is stabilized...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkv158
更新日期:2015-03-31 00:00:00
abstract::Targeted modulation of gene expression represents a valuable approach to understand the mechanisms governing gene regulation. In a therapeutic context, it can be exploited to selectively modify the aberrant expression of a disease-causing gene or to provide the target cells with a new function. Here, we have establish...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gky171
更新日期:2018-05-18 00:00:00
abstract::As a trial practical application, we have applied optimized microfabricated electrophoresis devices, combined with enzymatic mutation detection methods, to the determination of single nucleotide polymorphism (SNP) sites in the p53 suppressor gene. Using clinical samples, we have achieved robust assays with quality fac...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/28.9.e43
更新日期:2000-05-01 00:00:00
abstract::UV-irradiation (lambda = 254 nm) of liquid aqueous solutions of deoxyguanosine in the presence of oxygen at pH less than 7 causes an intensive degradation of nucleoside. The quantum yield estimated from A254 decrease for the reaction mixture was found to be 1.5X10(-4) at doses to 150 E/mole. The rate of A254 decrease ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/4.4.955
更新日期:1977-04-01 00:00:00
abstract::RNase J is a conserved ribonuclease that belongs to the β-CASP family of nucleases. It possesses both endo- and exo-ribonuclease activities, which play a key role in pre-rRNA maturation and mRNA decay. Here we report high-resolution crystal structures of Deinococcus radiodurans RNase J complexed with RNA or uridine 5'...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkv444
更新日期:2015-06-23 00:00:00
abstract::We have assessed the ability of nucleosomes to influence the formation of mammalian topoisomerase II-DNA complexes by mapping the sites of cleavage induced by four unrelated topoisomerase II inhibitors in naked versus nucleosome-reconstituted SV40 DNA. DNA fragments were reconstituted with histone octamers from HeLa c...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/18.15.4553
更新日期:1990-08-11 00:00:00
abstract::RJ2.2.5, a mutant derived from the human B-lymphoma cell, Raji, is unable to express the MHC class II genes because of a recessive transcriptional defect attributed to the lack of an activator function. We report the isolation of a RJ2.2.5 revertant, namely AR, in which the expression of the mRNAs encoded by these gen...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/21.3.381
更新日期:1993-02-11 00:00:00
abstract::Infection of Escherichia coli by a bacteriophage T4 regA, gene 44 double mutant leads to about a 7-fold increase in the amount of RNA ligase obtained after infection by wild-type phage. Using cells infected by the double mutant, RNA ligase was purified to homogeneity with a 20% yield. Unlike previous preparations of t...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/4.9.3175
更新日期:1977-09-01 00:00:00