Intronic sequence elements impede exon ligation and trigger a discard pathway that yields functional telomerase RNA in fission yeast.


:The fission yeast telomerase RNA (TER1) precursor harbors an intron immediately downstream from its mature 3' end. Unlike most introns, which are removed from precursor RNAs by the spliceosome in two sequential but tightly coupled transesterification reactions, TER1 only undergoes the first cleavage reaction during telomerase RNA maturation. The mechanism underlying spliceosome-mediated 3' end processing has remained unclear. We now demonstrate that a strong branch site (BS), a long distance to the 3' splice site (3' SS), and a weak polypyrimidine (Py) tract act synergistically to attenuate the transition from the first to the second step of splicing. The observation that a strong BS antagonizes the second step of splicing in the context of TER1 suggests that the BS-U2 snRNA interaction is disrupted after the first step and thus much earlier than previously thought. The slow transition from first to second step triggers the Prp22 DExD/H-box helicase-dependent rejection of the cleaved products and Prp43-dependent "discard" of the splicing intermediates. Our findings explain how the spliceosome can function in 3' end processing and provide new insights into the mechanism of splicing.


Genes Dev


Genes & development


Kannan R,Hartnett S,Voelker RB,Berglund JA,Staley JP,Baumann P




Has Abstract


2013-03-15 00:00:00














  • Nutrient-dependent control of RNA polymerase II elongation rate regulates specific gene expression programs by alternative polyadenylation.

    abstract::Transcription by RNA polymerase II (RNAPII) is a dynamic process with frequent variations in the elongation rate. However, the physiological relevance of variations in RNAPII elongation kinetics has remained unclear. Here we show in yeast that a RNAPII mutant that reduces the transcription elongation rate causes wides...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Yague-Sanz C,Vanrobaeys Y,Fernandez R,Duval M,Larochelle M,Beaudoin J,Berro J,Labbé S,Jacques PÉ,Bachand F

    更新日期:2020-07-01 00:00:00

  • Drosophila ORC specifically binds to ACE3, an origin of DNA replication control element.

    abstract::In the yeast Saccharomyces cerevisiae, sequence-specific DNA binding by the origin recognition complex (ORC) is responsible for selecting origins of DNA replication. In metazoans, origin selection is poorly understood and it is unknown whether specific DNA binding by metazoan ORC controls replication. To address this ...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Austin RJ,Orr-Weaver TL,Bell SP

    更新日期:1999-10-15 00:00:00

  • Raf-induced MMP9 disrupts tissue architecture of human breast cells in three-dimensional culture and is necessary for tumor growth in vivo.

    abstract::Organization into polarized three-dimensional structures defines whether epithelial cells are normal or malignant. In a model of morphogenesis, we show that inhibiting key signaling pathways in human breast cancer cells leads to "phenotypic reversion" of the malignant cells. Using architecture as an endpoint, we repor...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Beliveau A,Mott JD,Lo A,Chen EI,Koller AA,Yaswen P,Muschler J,Bissell MJ

    更新日期:2010-12-15 00:00:00

  • Regulation of splicing at an intermediate step in the formation of the spliceosome.

    abstract::In vivo experiments have demonstrated that the ribosomal protein L32 of Saccharomyces cerevisiae brings about the inhibition of splicing of the transcript of its own gene through an RNA structure comprised largely of the first exon. We now show that L32, itself, binds specifically to this RNA. Splicing of the RPL32 tr...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Vilardell J,Warner JR

    更新日期:1994-01-01 00:00:00

  • Direct induction of G1-specific transcripts following reactivation of the Cdc28 kinase in the absence of de novo protein synthesis.

    abstract::In Saccharomyces cerevisiae, the genes encoding the HO endonuclease, G1-specific cyclins CLN1 and CLN2, as well as most proteins involved in DNA synthesis, are periodically transcribed with maximal levels reached in late G1. For HO and the DNA replication genes, cell cycle stage-specific expression has been shown to b...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Marini NJ,Reed SI

    更新日期:1992-04-01 00:00:00

  • TRF1 is degraded by ubiquitin-mediated proteolysis after release from telomeres.

    abstract::Mammalian telomeres are coated by the sequence-specific, DNA-binding protein, TRF1, a negative regulator of telomere length. Previous results showed that ADP-ribosylation of TRF1 by tankyrase 1 released TRF1 from telomeres and promoted telomere elongation. We now show that loss of TRF1 from telomeres results in ubiqui...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Chang W,Dynek JN,Smith S

    更新日期:2003-06-01 00:00:00

  • Voltage-gated potassium channel EAG2 controls mitotic entry and tumor growth in medulloblastoma via regulating cell volume dynamics.

    abstract::Medulloblastoma (MB) is the most common pediatric CNS malignancy. We identify EAG2 as an overexpressed potassium channel in MBs across different molecular and histological subgroups. EAG2 knockdown not only impairs MB cell growth in vitro, but also reduces tumor burden in vivo and enhances survival in xenograft studie...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Huang X,Dubuc AM,Hashizume R,Berg J,He Y,Wang J,Chiang C,Cooper MK,Northcott PA,Taylor MD,Barnes MJ,Tihan T,Chen J,Hackett CS,Weiss WA,James CD,Rowitch DH,Shuman MA,Jan YN,Jan LY

    更新日期:2012-08-15 00:00:00

  • DOT1L regulates dystrophin expression and is critical for cardiac function.

    abstract::Histone methylation plays an important role in regulating gene expression. One such methylation occurs at Lys 79 of histone H3 (H3K79) and is catalyzed by the yeast DOT1 (disruptor of telomeric silencing) and its mammalian homolog, DOT1L. Previous studies have demonstrated that germline disruption of Dot1L in mice res...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Nguyen AT,Xiao B,Neppl RL,Kallin EM,Li J,Chen T,Wang DZ,Xiao X,Zhang Y

    更新日期:2011-02-01 00:00:00

  • Translational profiling of hypocretin neurons identifies candidate molecules for sleep regulation.

    abstract::Hypocretin (orexin; Hcrt)-containing neurons of the hypothalamus are essential for the normal regulation of sleep and wake behaviors and have been implicated in feeding, anxiety, depression, and reward. The absence of these neurons causes narcolepsy in humans and model organisms. However, little is known about the mol...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Dalal J,Roh JH,Maloney SE,Akuffo A,Shah S,Yuan H,Wamsley B,Jones WB,de Guzman Strong C,Gray PA,Holtzman DM,Heintz N,Dougherty JD

    更新日期:2013-03-01 00:00:00

  • Polycomb-mediated repression during terminal differentiation: what don't you want to be when you grow up?

    abstract::Chromatin-modifying enzymes are known to be critical components for the correct differentiation of embryonic stem cells into specific lineages, such as neurons. Recently, the role of Polycomb group proteins has been studied in the specification and differentiation of muscle stem cells. In this perspective, we review a...

    journal_title:Genes & development

    pub_type: 评论,杂志文章


    authors: Conerly ML,MacQuarrie KL,Fong AP,Yao Z,Tapscott SJ

    更新日期:2011-05-15 00:00:00

  • Biological functions of the ISWI chromatin remodeling complex NURF.

    abstract::The nucleosome remodeling factor (NURF) is one of several ISWI-containing protein complexes that catalyze ATP-dependent nucleosome sliding and facilitate transcription of chromatin in vitro. To establish the physiological requirements of NURF, and to distinguish NURF genetically from other ISWI-containing complexes, w...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Badenhorst P,Voas M,Rebay I,Wu C

    更新日期:2002-12-15 00:00:00

  • Changes in histone gene dosage alter transcription in yeast.

    abstract::Chromatin structure is believed to be important for a number of cellular processes, including transcription. However, the role of nucleosomes in transcription is not well understood. We have identified the yeast histone locus HTB1-HTB1, encoding histones H2A and H2B, as a suppressor of solo delta insertion mutations t...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Clark-Adams CD,Norris D,Osley MA,Fassler JS,Winston F

    更新日期:1988-02-01 00:00:00

  • A splicing enhancer exhibits both constitutive and regulated activities.

    abstract::The Drosophila proteins Transformer (Tra) and Transformer2 (Tra2) regulate the sex-specific alternative splicing of Drosophila doublesex (dsx) pre-mRNA by specifically binding to a splicing enhancer (dsx repeat element; dsxRE) located 300 nucleotides (nt) downstream from a female-specific 3' splice site. In this paper...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Tian M,Maniatis T

    更新日期:1994-07-15 00:00:00

  • SCH9, a gene of Saccharomyces cerevisiae that encodes a protein distinct from, but functionally and structurally related to, cAMP-dependent protein kinase catalytic subunits.

    abstract::A new gene, SCH9, was isolated from Saccharomyces cerevisiae by its ability to complement a cdc25ts mutation. Sequence analysis indicates that it encodes a 90,000-dalton protein with a carboxy-terminal domain homologous to yeast and mammalian cAMP-dependent protein kinase catalytic subunits. In addition to suppressing...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Toda T,Cameron S,Sass P,Wigler M

    更新日期:1988-05-01 00:00:00

  • DTL/CDT2 is essential for both CDT1 regulation and the early G2/M checkpoint.

    abstract::Checkpoint genes maintain genomic stability by arresting cells after DNA damage. Many of these genes also control cell cycle events in unperturbed cells. By conducting a screen for checkpoint genes in zebrafish, we found that dtl/cdt2 is an essential component of the early, radiation-induced G2/M checkpoint. We subseq...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Sansam CL,Shepard JL,Lai K,Ianari A,Danielian PS,Amsterdam A,Hopkins N,Lees JA

    更新日期:2006-11-15 00:00:00

  • Dorsal and neural expression of a tyrosine kinase-related Drosophila gene during embryonic development.

    abstract::Sequence analysis of an embryonic transcript of Drosophila predicts a tyrosine protein kinase-related gene. The prediction is based on several protein domains that are homologous to the functional domains of kinase-related oncogenes and several serine, threonine, and tyrosine protein kinases. For this reason, we named...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Haller J,Côté S,Brönner G,Jäckle H

    更新日期:1987-10-01 00:00:00

  • Drosophila lacking microRNA miR-278 are defective in energy homeostasis.

    abstract::The mechanisms that control energy homeostasis and tissue growth during development are closely linked through the insulin signal transduction pathway. Changes in the level of insulin and other hormones reflect the nutritional status of the animal to control circulating sugar levels and fat metabolism. Systemic defect...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Teleman AA,Maitra S,Cohen SM

    更新日期:2006-02-15 00:00:00

  • CHD4/Mi-2beta activity is required for the positioning of the mesoderm/neuroectoderm boundary in Xenopus.

    abstract::Experiments in Xenopus have illustrated the importance of extracellular morphogens for embryonic gene regulation in vertebrates. Much less is known about how induction leads to the correct positioning of boundaries; for example, between germ layers. Here we report that the neuroectoderm/mesoderm boundary is controlled...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Linder B,Mentele E,Mansperger K,Straub T,Kremmer E,Rupp RA

    更新日期:2007-04-15 00:00:00

  • Anti-diabetic rosiglitazone remodels the adipocyte transcriptome by redistributing transcription to PPARγ-driven enhancers.

    abstract::Rosiglitazone (rosi) is a powerful insulin sensitizer, but serious toxicities have curtailed its widespread clinical use. Rosi functions as a high-affinity ligand for peroxisome proliferator-activated receptor γ (PPARγ), the adipocyte-predominant nuclear receptor (NR). The classic model, involving binding of ligand to...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Step SE,Lim HW,Marinis JM,Prokesch A,Steger DJ,You SH,Won KJ,Lazar MA

    更新日期:2014-05-01 00:00:00

  • Yeast calcineurin regulates nuclear localization of the Crz1p transcription factor through dephosphorylation.

    abstract::Calcineurin, a Ca2+/calmodulin dependent protein phosphatase, regulates Ca2+-dependent processes in a wide variety of cells. In the yeast, Saccharomyces cerevisiae, calcineurin effects Ca2+-dependent changes in gene expression through regulation of the Crz1p transcription factor. We show here that calcineurin dephosph...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Stathopoulos-Gerontides A,Guo JJ,Cyert MS

    更新日期:1999-04-01 00:00:00

  • Keratinocyte growth factor is required for hair development but not for wound healing.

    abstract::Keratinocyte growth factor (KGF), also known as fibroblast growth factor 7 (FGF7), is synthesized by skin fibroblasts. However, its mitogenic activity is on skin keratinocytes, where it is the most potent growth factor identified thus far. To explore KGF's function in vivo, we used embryonic stem cell technology to ge...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Guo L,Degenstein L,Fuchs E

    更新日期:1996-01-15 00:00:00

  • Xenopus cdc7 function is dependent on licensing but not on XORC, XCdc6, or CDK activity and is required for XCdc45 loading.

    abstract::The assembly and disassembly of protein complexes at replication origins play a crucial role in the regulation of chromosomal DNA replication. The sequential binding of the origin recognition complex (ORC), Cdc6, and the minichromosome maintenance (MCM/P1) proteins produces a licensed replication origin. Before the in...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Jares P,Blow JJ

    更新日期:2000-06-15 00:00:00

  • Tandem AP-1-binding sites within the human beta-globin dominant control region function as an inducible enhancer in erythroid cells.

    abstract::A powerful enhancer has been mapped to an 18-bp DNA segment located 11 kb 5' to the human epsilon-globin gene within the dominant control or locus-activating region. This enhancer is inducible in K562 human erythroleukemia cells, increasing linked gamma-globin promoter/luciferase gene expression to 170-fold over an en...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Ney PA,Sorrentino BP,McDonagh KT,Nienhuis AW

    更新日期:1990-06-01 00:00:00

  • Smad proteins act in combination with synergistic and antagonistic regulators to target Dpp responses to the Drosophila mesoderm.

    abstract::Dorsal mesoderm induction in arthropods and ventral mesoderm induction in vertebrates are closely related processes that involve signals of the BMP family. In Drosophila, induction of visceral mesoderm, dorsal muscles, and the heart by Dpp is, at least in part, effected through the transcriptional activation and funct...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Xu X,Yin Z,Hudson JB,Ferguson EL,Frasch M

    更新日期:1998-08-01 00:00:00

  • Not just scaffolding: plectin regulates actin dynamics in cultured cells.

    abstract::Plectin, a major linker and scaffolding protein of the cytoskeleton, has been shown to be essential for the mechanical integrity of skin, skeletal muscle, and heart. Studying fibroblast and astroglial cell cultures derived from plectin (-/-) mice, we found that their actin cytoskeleton, including focal adhesion contac...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Andrä K,Nikolic B,Stöcher M,Drenckhahn D,Wiche G

    更新日期:1998-11-01 00:00:00

  • Disruption of retinoblastoma protein function by coexpression of its C pocket fragment.

    abstract::The growth suppression function of the retinoblastoma protein (RB) is mediated by its interaction with a variety of cellular proteins. RB contains at least two protein-binding pockets: the large A/B pocket, which interacts with E2F and the D-type cyclins, and the C pocket, which interacts with the nuclear c-Abl tyrosi...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Welch PJ,Wang JY

    更新日期:1995-01-01 00:00:00

  • A homeobox gene, PRESSED FLOWER, regulates lateral axis-dependent development of Arabidopsis flowers.

    abstract::It is postulated that the symmetric organization of plant lateral organs is based on two crossed axes, the abaxial-adaxial and the lateral axes. The PRESSED FLOWER (PRS) gene, the expression and function of which are dependent on the lateral axis, is reported in this study. In the prs mutant, growth of the lateral sep...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Matsumoto N,Okada K

    更新日期:2001-12-15 00:00:00

  • Genome-wide chromatin footprinting reveals changes in replication origin architecture induced by pre-RC assembly.

    abstract::Start sites of DNA replication are marked by the origin recognition complex (ORC), which coordinates Mcm2-7 helicase loading to form the prereplicative complex (pre-RC). Although pre-RC assembly is well characterized in vitro, the process is poorly understood within the local chromatin environment surrounding replicat...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Belsky JA,MacAlpine HK,Lubelsky Y,Hartemink AJ,MacAlpine DM

    更新日期:2015-01-15 00:00:00

  • Masquerade: a novel secreted serine protease-like molecule is required for somatic muscle attachment in the Drosophila embryo.

    abstract::Diverse developmental processes, such as neuronal growth cone migration and cell shape changes, are mediated by the interactions of cells with the extracellular matrix. We describe here a secreted molecule encoded by the Drosophila masquerade (mas) gene. Total loss of mas function causes defective muscle attachment. T...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Murugasu-Oei B,Rodrigues V,Yang X,Chia W

    更新日期:1995-01-15 00:00:00

  • Novel murine homeo box gene on chromosome 1 expressed in specific hematopoietic lineages and during embryogenesis.

    abstract::We describe here a new murine homeo box gene, denoted Hlx, which is expressed within specific hematopoietic lineages. The cDNA sequence indicates that Hlx differs markedly from known vertebrate homeo box genes, and linkage analysis of an interspecific murine backcross showed that it resides at a novel homeo box locus ...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Allen JD,Lints T,Jenkins NA,Copeland NG,Strasser A,Harvey RP,Adams JM

    更新日期:1991-04-01 00:00:00