The mechanisms of a mammalian splicing enhancer.

Abstract:

:Exonic splicing enhancer (ESE) sequences are bound by serine & arginine-rich (SR) proteins, which in turn enhance the recruitment of splicing factors. It was inferred from measurements of splicing around twenty years ago that Drosophila doublesex ESEs are bound stably by SR proteins, and that the bound proteins interact directly but with low probability with their targets. However, it has not been possible with conventional methods to demonstrate whether mammalian ESEs behave likewise. Using single molecule multi-colour colocalization methods to study SRSF1-dependent ESEs, we have found that that the proportion of RNA molecules bound by SRSF1 increases with the number of ESE repeats, but only a single molecule of SRSF1 is bound. We conclude that initial interactions between SRSF1 and an ESE are weak and transient, and that these limit the activity of a mammalian ESE. We tested whether the activation step involves the propagation of proteins along the RNA or direct interactions with 3' splice site components by inserting hexaethylene glycol or abasic RNA between the ESE and the target 3' splice site. These insertions did not block activation, and we conclude that the activation step involves direct interactions. These results support a model in which regulatory proteins bind transiently and in dynamic competition, with the result that each ESE in an exon contributes independently to the probability that an activator protein is bound and in close proximity to a splice site.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Jobbins AM,Reichenbach LF,Lucas CM,Hudson AJ,Burley GA,Eperon IC

doi

10.1093/nar/gky056

subject

Has Abstract

pub_date

2018-03-16 00:00:00

pages

2145-2158

issue

5

eissn

0305-1048

issn

1362-4962

pii

4829697

journal_volume

46

pub_type

杂志文章
  • Direct PCR sequencing with boronated nucleotides.

    abstract::A method is described to simultaneously amplify and sequence DNA using a new class of nucleotides containing boron. During the polymerase chain reaction, boron-modified nucleotides, i.e. 2'-deoxynucleoside 5'-alpha-[P-borano]-triphosphates, are incorporated into the product DNA. The boranophosphate linkages are resist...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/25.8.1611

    authors: Porter KW,Briley JD,Shaw BR

    更新日期:1997-04-15 00:00:00

  • Protection of (dA.dT) cluster regions in the DNAase I cleavage of DNA by specific interaction with netropsin.

    abstract::The specific DNA binding ligand netropsin selectively blocks dA-dT base pairs in clusters containing two or more consecutive thymine residues at the dNAase I cleavage sites of DNA. Using CD and UV absorption measurements it is shown, that at various ratios of netropsin to nucleotide concentrations and even at satuatio...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/8.13.2999

    authors: Zimmer C,Luck G,Nüske R

    更新日期:1980-07-11 00:00:00

  • Promoter-enhancer looping at the PPARγ2 locus during adipogenic differentiation requires the Prmt5 methyltransferase.

    abstract::PPARγ2 is a critical lineage-determining transcription factor that is essential for adipogenic differentiation. Here we report characterization of the three-dimensional structure of the PPARγ2 locus after the onset of adipogenic differentiation and the mechanisms by which it forms. We identified a differentiation-depe...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkw129

    authors: LeBlanc SE,Wu Q,Lamba P,Sif S,Imbalzano AN

    更新日期:2016-06-20 00:00:00

  • Denaturation maps of DNA: experimental and theoretical maps of phiX174 DNA.

    abstract::A formaldehyde denaturation map of the replicative form of phiX174 DNA is obtained. The RFI DNA was converted into a linear state by restriction endonuclease pst I which introduces into this DNA a single double-stranded break. The map has four clear-cut peaks. Their positions excellently correlate with the peak positi...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/5.7.2493

    authors: Karataev GI,Permogorov VI,Vologodskii AV,Frank-Kamenetskii MD

    更新日期:1978-07-01 00:00:00

  • DNA double-strand break repair in cell-free extracts from Ku80-deficient cells: implications for Ku serving as an alignment factor in non-homologous DNA end joining.

    abstract::Non-homologous DNA end joining (NHEJ) is considered the major pathway of double-strand break (DSB) repair in mammalian cells and depends, among other things, on the DNA end-binding Ku70/80 hetero-dimer. To investigate the function of Ku in NHEJ we have compared the ability of cell-free extracts from wild-type CHO-K1 c...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/28.13.2585

    authors: Feldmann E,Schmiemann V,Goedecke W,Reichenberger S,Pfeiffer P

    更新日期:2000-07-01 00:00:00

  • Global translation inhibition yields condition-dependent de-repression of ribosome biogenesis mRNAs.

    abstract::Ribosome biogenesis (RiBi) is an extremely energy intensive process that is critical for gene expression. It is thus highly regulated, including through the tightly coordinated expression of over 200 RiBi genes by positive and negative transcriptional regulators. We investigated RiBi regulation as cells initiated meio...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkz231

    authors: Cheng Z,Brar GA

    更新日期:2019-06-04 00:00:00

  • Cpf1 protein induced bending of yeast centromere DNA element I.

    abstract::The centromere complex is a multicomponent structure essential for faithful chromosome transmission. Here we show that the S. cerevisiae centromere protein Cpf1 bends centromere DNA element I (CDEI) with the bend angle ranging from 66 degrees to 71 degrees. CDEI DNA sequences that carry point mutations which lead to r...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/21.20.4726

    authors: Niedenthal RK,Sen-Gupta M,Wilmen A,Hegemann JH

    更新日期:1993-10-11 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

  • Complete sequence of the amphioxus (Branchiostoma lanceolatum) mitochondrial genome: relations to vertebrates.

    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

    authors: Spruyt N,Delarbre C,Gachelin G,Laudet V

    更新日期:1998-07-01 00:00:00

  • Identification of a novel epigenetic regulatory region within the pluripotency associated microRNA cluster, EEmiRC.

    abstract::The miR-290 cluster is expressed in embryonic stem cells (ESCs) and is important for the maintenance of pluripotency, but little is known about the mechanisms regulating the early embryonic microRNA cluster (EEmiRC) expression. Here we report the identification of a 332-bp intragenic enhancer (IE) able to modulate the...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkq1344

    authors: Tata PR,Tata NR,Kühl M,Sirbu IO

    更新日期:2011-05-01 00:00:00

  • A novel occluded RNA recognition motif in Prp24 unwinds the U6 RNA internal stem loop.

    abstract::The essential splicing factor Prp24 contains four RNA Recognition Motif (RRM) domains, and functions to anneal U6 and U4 RNAs during spliceosome assembly. Here, we report the structure and characterization of the C-terminal RRM4. This domain adopts a novel non-canonical RRM fold with two additional flanking α-helices ...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkr455

    authors: Martin-Tumasz S,Richie AC,Clos LJ 2nd,Brow DA,Butcher SE

    更新日期:2011-09-01 00:00:00

  • A new nomenclature for the cytoplasmic ribosomal proteins of Saccharomyces cerevisiae.

    abstract::The availability of the complete sequence of the Saccharomyces cerevisiae genome has allowed a comprehensive analysis of the genes encoding cytoplasmic ribosomal proteins in this organism. On the basis of this complete inventory a new nomenclature for the yeast ribosomal proteins is presented. ...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/25.24.4872

    authors: Mager WH,Planta RJ,Ballesta JG,Lee JC,Mizuta K,Suzuki K,Warner JR,Woolford J

    更新日期:1997-12-15 00:00:00

  • Site-specific modification of the lactose operator with acetylaminofluorene.

    abstract::We have synthesized the tetradecamer GAGCXGATAACAAG containing a part of the sequence of the lactose operator. A guanine base in the sequence is replaced by the adduct of the carcinogen 2-acetylaminofluorene with guanine. Under the standard conditions of de-protection, the fluorene moiety is lost, leaving behind a gua...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/11.15.5093

    authors: Stöhrer G,Osband JA,Alvarado-Urbina G

    更新日期:1983-08-11 00:00:00

  • A new method of representing DNA sequences which combines ease of visual analysis with machine readability.

    abstract::A new method of representing DNA sequences has been devised which is termed stave projection. Compared with other formats for showing the base sequences of DNA, this method greatly enhances the ease of visual analysis of the sequences of bases and it is also in a machine readable form. Using this method it is possible...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/14.1.509

    authors: Cowin JE,Jellis CH,Rickwood D

    更新日期:1986-01-10 00:00:00

  • A nascent micronuclear pseudogene in the ciliate Euplotes crassus.

    abstract::The macronuclear genome of Euplotes crassus contains two different genes, EFA1 and EFA2, encoding EF-1alpha proteins. They are derived from micronuclear precursors in the course of a sexual process termed conjugation. We have found that two apparent micronuclear precursors exist for EFA1. They differ in their potentia...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/24.16.3195

    authors: Florian V,Klein A

    更新日期:1996-08-15 00:00:00

  • Recognition of the 70S ribosome and polysome by the RNA degradosome in Escherichia coli.

    abstract::The RNA degradosome is a multi-enzyme assembly that contributes to key processes of RNA metabolism, and it engages numerous partners in serving its varied functional roles. Small domains within the assembly recognize collectively a diverse range of macromolecules, including the core protein components, the cytoplasmic...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gks739

    authors: Tsai YC,Du D,Domínguez-Malfavón L,Dimastrogiovanni D,Cross J,Callaghan AJ,García-Mena J,Luisi BF

    更新日期:2012-11-01 00:00:00

  • VLDP web server: a powerful geometric tool for analysing protein structures in their environment.

    abstract::Protein structures are an ensemble of atoms determined experimentally mostly by X-ray crystallography or Nuclear Magnetic Resonance. Studying 3D protein structures is a key point for better understanding protein function at a molecular level. We propose a set of accurate tools, for analysing protein structures, based ...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkt509

    authors: Esque J,Léonard S,de Brevern AG,Oguey C

    更新日期:2013-07-01 00:00:00

  • The high mobility group A2 protein epigenetically silences the Cdh1 gene during epithelial-to-mesenchymal transition.

    abstract::The loss of the tumour suppressor E-cadherin (Cdh1) is a key event during tumourigenesis and epithelial-mesenchymal transition (EMT). Transforming growth factor-β (TGFβ) triggers EMT by inducing the expression of non-histone chromatin protein High Mobility Group A2 (HMGA2). We have previously shown that HMGA2, togethe...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gku1293

    authors: Tan EJ,Kahata K,Idås O,Thuault S,Heldin CH,Moustakas A

    更新日期:2015-01-01 00:00:00

  • Nucleotide sequence from the coding region of rabbit beta-globin messenger RNA.

    abstract::A sequence of 89 nucleotides from rabbit beta-globin mRNA has been determined and is shown to code for residues 107 to 137 of the beta-globin protein. In addition, a sequence heterogeneity has been identified within this 89 nucleotide long sequence which corresponds to a known polymorphic variant of rabbit beta-globin...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/3.7.1811

    authors: Proudfoot NJ

    更新日期:1976-07-01 00:00:00

  • Rational engineering of the Neurospora VS ribozyme to allow substrate recognition via different kissing-loop interactions.

    abstract::The Neurospora VS ribozyme is a catalytic RNA that has the unique ability to specifically recognize and cleave a stem-loop substrate through formation of a highly stable kissing-loop interaction (KLI). In order to explore the engineering potential of the VS ribozyme to cleave alternate substrates, we substituted the w...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkw401

    authors: Lacroix-Labonté J,Girard N,Dagenais P,Legault P

    更新日期:2016-08-19 00:00:00

  • Increased erythroid-specific expression of a mutated HPFH gamma-globin promoter requires the erythroid factor NFE-1.

    abstract::The -175 T greater than C mutation in the promoter of the A gamma- or G gamma-globin gene causes a 50-100 fold increase of the expression of the respective gene in adult erythroid cells (Hereditary Persistence of Fetal Hemoglobin). We show here that this mutation increases 3-9 fold the expression of a gamma-CAT report...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/17.14.5509

    authors: Nicolis S,Ronchi A,Malgaretti N,Mantovani R,Giglioni B,Ottolenghi S

    更新日期:1989-07-25 00:00:00

  • New rapid methods for DNA sequencing based in exonuclease III digestion followed by repair synthesis.

    abstract::We describe improve enzymatic methods for sequencing method for sequencing DNA. They are based on partial digestion of duplex DNA with exonuclease III to produce DNA molecules with 3' ends shortened to varying lengths, followed by repair synthesis to extend and label the 3' ends. After asymmetrical cleavage of the DNA...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/10.6.2065

    authors: Guo LH,Wu R

    更新日期:1982-03-25 00:00:00

  • Functional characterization of two human MutY homolog (hMYH) missense mutations (R227W and V232F) that lie within the putative hMSH6 binding domain and are associated with hMYH polyposis.

    abstract::The base excision repair DNA glycosylase MutY homolog (MYH) is responsible for removing adenines misincorporated into DNA opposite guanine or 7,8-dihydro-8-oxo-guanine (8-oxoG), thereby preventing G:C to T:A mutations. Biallelic germline mutations in the human MYH gene predispose individuals to multiple colorectal ade...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gki209

    authors: Bai H,Jones S,Guan X,Wilson TM,Sampson JR,Cheadle JP,Lu AL

    更新日期:2005-01-26 00:00:00

  • Circular chromosomal DNA in the sulfur-dependent archaebacterium Sulfolobus acidocaldarius.

    abstract::The shape of the chromosomal DNA of the sulfur-dependent archaebacterium Sulfolobus acidocaldarius was analyzed by the pulsed-field gel electrophoresis(PFGE). S.acidocaldarius DNA digested with Notl showed two DNA bands at around 1.0 Mbp and 2.1 Mbp. Notl-linking clones were isolated from the library of S.acidocaldari...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/18.5.1133

    authors: Yamagishi A,Oshima T

    更新日期:1990-03-11 00:00:00

  • The GAA*TTC triplet repeat expanded in Friedreich's ataxia impedes transcription elongation by T7 RNA polymerase in a length and supercoil dependent manner.

    abstract::Large expansions of the trinucleotide repeat GAA*TTC within the first intron of the X25 (frataxin) gene cause Friedreich's ataxia, the most common inherited ataxia. Expansion leads to reduced levels of frataxin mRNA in affected individuals. Here we show that GAA*TTC tracts, in the absence of any other frataxin gene se...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/28.14.2815

    authors: Grabczyk E,Usdin K

    更新日期:2000-07-15 00:00:00

  • The nucleotide sequence of the ubiquitous repetitive DNA sequence B1 complementary to the most abundant class of mouse fold-back RNA.

    abstract::Three copies of a highly repetitive DNA sequence B1 which is complementary to the most abundant class of mouse fold-back RNA have been cloned in pBR322 plasmid and sequenced by the method of Maxam and Gilbert. All the three have a length of about 130 base pairs and are very similar in their base sequence. The deviatio...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/8.6.1201

    authors: Krayev AS,Kramerov DA,Skryabin KG,Ryskov AP,Bayev AA,Georgiev GP

    更新日期:1980-03-25 00:00:00

  • Oligonucleotide mutagenesis of the lacPUV5 promoter.

    abstract::Synthetic oligonucleotides were used to introduce mutations into the lacPUV5 promoter. Four mutations were obtained at positions -13, -14, and -15, with respect to the transcriptional start site. The effects of these mutations were measured in vivo and the results are discussed with respect to the consensus sequence a...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/12.9.4011

    authors: Munson LM,Mandecki W,Caruthers MH,Reznikoff WS

    更新日期:1984-05-11 00:00:00

  • Two-dimensional gel analysis of rolling circle replication in the presence and absence of bacteriophage T4 primase.

    abstract::The rolling circle DNA replication structures generated by the in vitro phage T4 replication system were analyzed using two-dimensional agarose gels. Replication structures were generated in the presence or absence of T4 primase (gp61), permitting the analysis of replication forks with either duplex or single-stranded...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/24.11.2166

    authors: Belanger KG,Mirzayan C,Kreuzer HE,Alberts BM,Kreuzer KN

    更新日期:1996-06-01 00:00:00

  • Unusual duplex formation in purine rich oligodeoxyribonucleotides.

    abstract::The purine rich oligodeoxyribonucleotides 1C, d(ATGACGGAATA) and 2C, d(ATGAGCGAATA) alone exhibit highly cooperative melting transitions. Analysis of the concentration dependence of melting, and electrophoretic studies indicate that these oligomers can form an unusual purine rich offset double helix. The unusual duple...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/16.11.5137

    authors: Wilson WD,Dotrong MH,Zuo ET,Zon G

    更新日期:1988-06-10 00:00:00

  • d(GA x TC)(n) microsatellite DNA sequences enhance homologous DNA recombination in SV40 minichromosomes.

    abstract::The genomic distribution of the abundant eukaryotic d(GA x TC)(n) DNA microsatellite suggests that it could contribute to DNA recombination. Here, it is shown that this type of microsatellite DNA sequence enhances DNA recombination in SV40 minichromosomes, the rate of homologous DNA recombination increasing by as much...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/28.23.4617

    authors: Benet A,Mollà G,Azorín F

    更新日期:2000-12-01 00:00:00