The CUGBP2 splicing factor regulates an ensemble of branchpoints from perimeter binding sites with implications for autoregulation.

Abstract:

:Alternative pre-mRNA splicing adjusts the transcriptional output of the genome by generating related mRNAs from a single primary transcript, thereby expanding protein diversity. A fundamental unanswered question is how splicing factors achieve specificity in the selection of target substrates despite the recognition of information-poor sequence motifs. The CUGBP2 splicing regulator plays a key role in the brain region-specific silencing of the NI exon of the NMDA R1 receptor. However, the sequence motifs utilized by this factor for specific target exon selection and its role in splicing silencing are not understood. Here, we use chemical modification footprinting to map the contact sites of CUGBP2 to GU-rich motifs closely positioned at the boundaries of the branch sites of the NI exon, and we demonstrate a mechanistic role for this specific arrangement of motifs for the regulation of branchpoint formation. General support for a branch site-perimeter-binding model is indicated by the identification of a group of novel target exons with a similar configuration of motifs that are silenced by CUGBP2. These results reveal an autoregulatory role for CUGBP2 as indicated by its direct interaction with functionally significant RNA motifs surrounding the branch sites upstream of exon 6 of the CUGBP2 transcript itself. The perimeter-binding model explains how CUGBP2 can effectively embrace the branch site region to achieve the specificity needed for the selection of exon targets and the fine-tuning of alternative splicing patterns.

journal_name

PLoS Genet

journal_title

PLoS genetics

authors

Dembowski JA,Grabowski PJ

doi

10.1371/journal.pgen.1000595

subject

Has Abstract

pub_date

2009-08-01 00:00:00

pages

e1000595

issue

8

eissn

1553-7390

issn

1553-7404

journal_volume

5

pub_type

杂志文章
  • Extensive Regulation of Diurnal Transcription and Metabolism by Glucocorticoids.

    abstract::Altered daily patterns of hormone action are suspected to contribute to metabolic disease. It is poorly understood how the adrenal glucocorticoid hormones contribute to the coordination of daily global patterns of transcription and metabolism. Here, we examined diurnal metabolite and transcriptome patterns in a zebraf...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1006512

    authors: Weger BD,Weger M,Görling B,Schink A,Gobet C,Keime C,Poschet G,Jost B,Krone N,Hell R,Gachon F,Luy B,Dickmeis T

    更新日期:2016-12-12 00:00:00

  • Multifaceted genome control by Set1 Dependent and Independent of H3K4 methylation and the Set1C/COMPASS complex.

    abstract::Histone modifiers are critical regulators of chromatin-based processes in eukaryotes. The histone methyltransferase Set1, a component of the Set1C/COMPASS complex, catalyzes the methylation at lysine 4 of histone H3 (H3K4me), a hallmark of euchromatin. Here, we show that the fission yeast Schizosaccharomyces pombe Set...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1004740

    authors: Mikheyeva IV,Grady PJ,Tamburini FB,Lorenz DR,Cam HP

    更新日期:2014-10-30 00:00:00

  • OSD1 promotes meiotic progression via APC/C inhibition and forms a regulatory network with TDM and CYCA1;2/TAM.

    abstract::Cell cycle control is modified at meiosis compared to mitosis, because two divisions follow a single DNA replication event. Cyclin-dependent kinases (CDKs) promote progression through both meiosis and mitosis, and a central regulator of their activity is the APC/C (Anaphase Promoting Complex/Cyclosome) that is especia...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1002865

    authors: Cromer L,Heyman J,Touati S,Harashima H,Araou E,Girard C,Horlow C,Wassmann K,Schnittger A,De Veylder L,Mercier R

    更新日期:2012-01-01 00:00:00

  • Heat-induced release of epigenetic silencing reveals the concealed role of an imprinted plant gene.

    abstract::Epigenetic mechanisms suppress the transcription of transposons and DNA repeats; however, this suppression can be transiently released under prolonged heat stress. Here we show that the Arabidopsis thaliana imprinted gene SDC, which is silent during vegetative growth due to DNA methylation, is activated by heat and co...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1004806

    authors: Sanchez DH,Paszkowski J

    更新日期:2014-11-20 00:00:00

  • Loss of the DNA methyltransferase MET1 Induces H3K9 hypermethylation at PcG target genes and redistribution of H3K27 trimethylation to transposons in Arabidopsis thaliana.

    abstract::Dimethylation of histone H3 lysine 9 (H3K9m2) and trimethylation of histone H3 lysine 27 (H3K27m3) are two hallmarks of transcriptional repression in many organisms. In Arabidopsis thaliana, H3K27m3 is targeted by Polycomb Group (PcG) proteins and is associated with silent protein-coding genes, while H3K9m2 is correla...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1003062

    authors: Deleris A,Stroud H,Bernatavichute Y,Johnson E,Klein G,Schubert D,Jacobsen SE

    更新日期:2012-01-01 00:00:00

  • DNA methylation dynamics in human induced pluripotent stem cells over time.

    abstract::Epigenetic reprogramming is a critical event in the generation of induced pluripotent stem cells (iPSCs). Here, we determined the DNA methylation profiles of 22 human iPSC lines derived from five different cell types (human endometrium, placental artery endothelium, amnion, fetal lung fibroblast, and menstrual blood c...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1002085

    authors: Nishino K,Toyoda M,Yamazaki-Inoue M,Fukawatase Y,Chikazawa E,Sakaguchi H,Akutsu H,Umezawa A

    更新日期:2011-05-01 00:00:00

  • The role of ROC75 as a daytime component of the circadian oscillator in Chlamydomonas reinhardtii.

    abstract::The circadian clocks in chlorophyte algae have been studied in two model organisms, Chlamydomonas reinhardtii and Ostreococcus tauri. These studies revealed that the chlorophyte clocks include some genes that are homologous to those of the angiosperm circadian clock. However, the genetic network architectures of the c...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1008814

    authors: Matsuo T,Iida T,Ohmura A,Gururaj M,Kato D,Mutoh R,Ihara K,Ishiura M

    更新日期:2020-06-17 00:00:00

  • Mis-spliced transcripts of nicotinic acetylcholine receptor alpha6 are associated with field evolved spinosad resistance in Plutella xylostella (L.).

    abstract::The evolution of insecticide resistance is a global constraint to agricultural production. Spinosad is a new, low-environmental-risk insecticide that primarily targets nicotinic acetylcholine receptors (nAChR) and is effective against a wide range of pest species. However, after only a few years of application, field ...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1000802

    authors: Baxter SW,Chen M,Dawson A,Zhao JZ,Vogel H,Shelton AM,Heckel DG,Jiggins CD

    更新日期:2010-01-01 00:00:00

  • A latent pro-survival function for the mir-290-295 cluster in mouse embryonic stem cells.

    abstract::MicroRNAs (miRNAs) post-transcriptionally regulate the expression of thousands of distinct mRNAs. While some regulatory interactions help to maintain basal cellular functions, others are likely relevant in more specific settings, such as response to stress. Here we describe such a role for the mir-290-295 cluster, the...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1002054

    authors: Zheng GX,Ravi A,Calabrese JM,Medeiros LA,Kirak O,Dennis LM,Jaenisch R,Burge CB,Sharp PA

    更新日期:2011-05-01 00:00:00

  • Environmental and genetic determinants of colony morphology in yeast.

    abstract::Nutrient stresses trigger a variety of developmental switches in the budding yeast Saccharomyces cerevisiae. One of the least understood of such responses is the development of complex colony morphology, characterized by intricate, organized, and strain-specific patterns of colony growth and architecture. The genetic ...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1000823

    authors: Granek JA,Magwene PM

    更新日期:2010-01-22 00:00:00

  • Overlapping and non-overlapping functions of condensins I and II in neural stem cell divisions.

    abstract::During development of the cerebral cortex, neural stem cells (NSCs) divide symmetrically to proliferate and asymmetrically to generate neurons. Although faithful segregation of mitotic chromosomes is critical for NSC divisions, its fundamental mechanism remains unclear. A class of evolutionarily conserved protein comp...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1004847

    authors: Nishide K,Hirano T

    更新日期:2014-12-04 00:00:00

  • Systemic Regulation of RAS/MAPK Signaling by the Serotonin Metabolite 5-HIAA.

    abstract::Human cancer is caused by the interplay of mutations in oncogenes and tumor suppressor genes and inherited variations in cancer susceptibility genes. While many of the tumor initiating mutations are well characterized, the effect of genetic background variation on disease onset and progression is less understood. We h...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1005236

    authors: Schmid T,Snoek LB,Fröhli E,van der Bent ML,Kammenga J,Hajnal A

    更新日期:2015-05-15 00:00:00

  • Anatomic demarcation by positional variation in fibroblast gene expression programs.

    abstract::Fibroblasts are ubiquitous mesenchymal cells with many vital functions during development, tissue repair, and disease. Fibroblasts from different anatomic sites have distinct and characteristic gene expression patterns, but the principles that govern their molecular specialization are poorly understood. Spatial organi...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.0020119

    authors: Rinn JL,Bondre C,Gladstone HB,Brown PO,Chang HY

    更新日期:2006-07-01 00:00:00

  • CTCF genomic binding sites in Drosophila and the organisation of the bithorax complex.

    abstract::Insulator or enhancer-blocking elements are proposed to play an important role in the regulation of transcription by preventing inappropriate enhancer/promoter interaction. The zinc-finger protein CTCF is well studied in vertebrates as an enhancer blocking factor, but Drosophila CTCF has only been characterised recent...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.0030112

    authors: Holohan EE,Kwong C,Adryan B,Bartkuhn M,Herold M,Renkawitz R,Russell S,White R

    更新日期:2007-07-01 00:00:00

  • Glycine and Folate Ameliorate Models of Congenital Sideroblastic Anemia.

    abstract::Sideroblastic anemias are acquired or inherited anemias that result in a decreased ability to synthesize hemoglobin in red blood cells and result in the presence of iron deposits in the mitochondria of red blood cell precursors. A common subtype of congenital sideroblastic anemia is due to autosomal recessive mutation...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1005783

    authors: Fernández-Murray JP,Prykhozhij SV,Dufay JN,Steele SL,Gaston D,Nasrallah GK,Coombs AJ,Liwski RS,Fernandez CV,Berman JN,McMaster CR

    更新日期:2016-01-28 00:00:00

  • BOD1 Is Required for Cognitive Function in Humans and Drosophila.

    abstract::Here we report a stop-mutation in the BOD1 (Biorientation Defective 1) gene, which co-segregates with intellectual disability in a large consanguineous family, where individuals that are homozygous for the mutation have no detectable BOD1 mRNA or protein. The BOD1 protein is required for proper chromosome segregation,...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1006022

    authors: Esmaeeli-Nieh S,Fenckova M,Porter IM,Motazacker MM,Nijhof B,Castells-Nobau A,Asztalos Z,Weißmann R,Behjati F,Tzschach A,Felbor U,Scherthan H,Sayfati SM,Ropers HH,Kahrizi K,Najmabadi H,Swedlow JR,Schenck A,Kuss AW

    更新日期:2016-05-11 00:00:00

  • CorE from Myxococcus xanthus is a copper-dependent RNA polymerase sigma factor.

    abstract::The dual toxicity/essentiality of copper forces cells to maintain a tightly regulated homeostasis for this metal in all living organisms, from bacteria to humans. Consequently, many genes have previously been reported to participate in copper detoxification in bacteria. Myxococcus xanthus, a prokaryote, encodes many p...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1002106

    authors: Gómez-Santos N,Pérez J,Sánchez-Sutil MC,Moraleda-Muñoz A,Muñoz-Dorado J

    更新日期:2011-06-01 00:00:00

  • Genome-wide identification of susceptibility alleles for viral infections through a population genetics approach.

    abstract::Viruses have exerted a constant and potent selective pressure on human genes throughout evolution. We utilized the marks left by selection on allele frequency to identify viral infection-associated allelic variants. Virus diversity (the number of different viruses in a geographic region) was used to measure virus-driv...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1000849

    authors: Fumagalli M,Pozzoli U,Cagliani R,Comi GP,Bresolin N,Clerici M,Sironi M

    更新日期:2010-02-19 00:00:00

  • Recruitment of the Ulp2 protease to the inner kinetochore prevents its hyper-sumoylation to ensure accurate chromosome segregation.

    abstract::The kinetochore is the central molecular machine that drives chromosome segregation in all eukaryotes. Genetic studies have suggested that protein sumoylation plays a role in regulating the inner kinetochore; however, the mechanism remains elusive. Here, we show that Saccharomyces cerevisiae Ulp2, an evolutionarily co...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1008477

    authors: Suhandynata RT,Quan Y,Yang Y,Yuan WT,Albuquerque CP,Zhou H

    更新日期:2019-11-20 00:00:00

  • High-resolution mapping of expression-QTLs yields insight into human gene regulation.

    abstract::Recent studies of the HapMap lymphoblastoid cell lines have identified large numbers of quantitative trait loci for gene expression (eQTLs). Reanalyzing these data using a novel Bayesian hierarchical model, we were able to create a surprisingly high-resolution map of the typical locations of sites that affect mRNA lev...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1000214

    authors: Veyrieras JB,Kudaravalli S,Kim SY,Dermitzakis ET,Gilad Y,Stephens M,Pritchard JK

    更新日期:2008-10-01 00:00:00

  • A discrete transition zone organizes the topological and regulatory autonomy of the adjacent tfap2c and bmp7 genes.

    abstract::Despite the well-documented role of remote enhancers in controlling developmental gene expression, the mechanisms that allocate enhancers to genes are poorly characterized. Here, we investigate the cis-regulatory organization of the locus containing the Tfap2c and Bmp7 genes in vivo, using a series of engineered chrom...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1004897

    authors: Tsujimura T,Klein FA,Langenfeld K,Glaser J,Huber W,Spitz F

    更新日期:2015-01-08 00:00:00

  • Metabolites of lactic acid bacteria present in fermented foods are highly potent agonists of human hydroxycarboxylic acid receptor 3.

    abstract::The interplay of microbiota and the human host is physiologically crucial in health and diseases. The beneficial effects of lactic acid bacteria (LAB), permanently colonizing the human intestine or transiently obtained from food, have been extensively reported. However, the molecular understanding of how LAB modulate ...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1008145

    authors: Peters A,Krumbholz P,Jäger E,Heintz-Buschart A,Çakir MV,Rothemund S,Gaudl A,Ceglarek U,Schöneberg T,Stäubert C

    更新日期:2019-05-23 00:00:00

  • Graded Nodal/Activin signaling titrates conversion of quantitative phospho-Smad2 levels into qualitative embryonic stem cell fate decisions.

    abstract::Nodal and Activin are morphogens of the TGFbeta superfamily of signaling molecules that direct differential cell fate decisions in a dose- and distance-dependent manner. During early embryonic development the Nodal/Activin pathway is responsible for the specification of mesoderm, endoderm, node, and mesendoderm. In co...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1002130

    authors: Lee KL,Lim SK,Orlov YL,Yit le Y,Yang H,Ang LT,Poellinger L,Lim B

    更新日期:2011-06-01 00:00:00

  • Mismatch repair balances leading and lagging strand DNA replication fidelity.

    abstract::The two DNA strands of the nuclear genome are replicated asymmetrically using three DNA polymerases, α, δ, and ε. Current evidence suggests that DNA polymerase ε (Pol ε) is the primary leading strand replicase, whereas Pols α and δ primarily perform lagging strand replication. The fact that these polymerases differ in...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1003016

    authors: Lujan SA,Williams JS,Pursell ZF,Abdulovic-Cui AA,Clark AB,Nick McElhinny SA,Kunkel TA

    更新日期:2012-01-01 00:00:00

  • Recurrent loss of specific introns during angiosperm evolution.

    abstract::Numerous instances of presence/absence variations for introns have been documented in eukaryotes, and some cases of recurrent loss of the same intron have been suggested. However, there has been no comprehensive or phylogenetically deep analysis of recurrent intron loss. Of 883 cases of intron presence/absence variati...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1004843

    authors: Wang H,Devos KM,Bennetzen JL

    更新日期:2014-12-04 00:00:00

  • The fitness effects of random mutations in single-stranded DNA and RNA bacteriophages.

    abstract::Mutational fitness effects can be measured with relatively high accuracy in viruses due to their small genome size, which facilitates full-length sequencing and genetic manipulation. Previous work has shown that animal and plant RNA viruses are very sensitive to mutation. Here, we characterize mutational fitness effec...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1000742

    authors: Domingo-Calap P,Cuevas JM,Sanjuán R

    更新日期:2009-11-01 00:00:00

  • Identifying signatures of natural selection in Tibetan and Andean populations using dense genome scan data.

    abstract::High-altitude hypoxia (reduced inspired oxygen tension due to decreased barometric pressure) exerts severe physiological stress on the human body. Two high-altitude regions where humans have lived for millennia are the Andean Altiplano and the Tibetan Plateau. Populations living in these regions exhibit unique circula...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1001116

    authors: Bigham A,Bauchet M,Pinto D,Mao X,Akey JM,Mei R,Scherer SW,Julian CG,Wilson MJ,López Herráez D,Brutsaert T,Parra EJ,Moore LG,Shriver MD

    更新日期:2010-09-09 00:00:00

  • Genetic variants influence on the placenta regulatory landscape.

    abstract::From genomic association studies, quantitative trait loci analysis, and epigenomic mapping, it is evident that significant efforts are necessary to define genetic-epigenetic interactions and understand their role in disease susceptibility and progression. For this reason, an analysis of the effects of genetic variatio...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1007785

    authors: Delahaye F,Do C,Kong Y,Ashkar R,Salas M,Tycko B,Wapner R,Hughes F

    更新日期:2018-11-19 00:00:00

  • Ranking and characterization of established BMI and lipid associated loci as candidates for gene-environment interactions.

    abstract::Phenotypic variance heterogeneity across genotypes at a single nucleotide polymorphism (SNP) may reflect underlying gene-environment (G×E) or gene-gene interactions. We modeled variance heterogeneity for blood lipids and BMI in up to 44,211 participants and investigated relationships between variance effects (Pv), G×E...

    journal_title:PLoS genetics

    pub_type: 杂志文章,meta分析

    doi:10.1371/journal.pgen.1006812

    authors: Shungin D,Deng WQ,Varga TV,Luan J,Mihailov E,Metspalu A,GIANT Consortium.,Morris AP,Forouhi NG,Lindgren C,Magnusson PKE,Pedersen NL,Hallmans G,Chu AY,Justice AE,Graff M,Winkler TW,Rose LM,Langenberg C,Cupples LA,R

    更新日期:2017-06-14 00:00:00

  • Analysis of the genetic basis of disease in the context of worldwide human relationships and migration.

    abstract::Genetic diversity across different human populations can enhance understanding of the genetic basis of disease. We calculated the genetic risk of 102 diseases in 1,043 unrelated individuals across 51 populations of the Human Genome Diversity Panel. We found that genetic risk for type 2 diabetes and pancreatic cancer d...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1003447

    authors: Corona E,Chen R,Sikora M,Morgan AA,Patel CJ,Ramesh A,Bustamante CD,Butte AJ

    更新日期:2013-05-01 00:00:00