SMG6 interacts with the exon junction complex via two conserved EJC-binding motifs (EBMs) required for nonsense-mediated mRNA decay.

Abstract:

:Nonsense-mediated mRNA decay (NMD) is a quality control mechanism that detects and degrades mRNAs containing premature stop codons (PTCs). In vertebrates, PTCs trigger efficient NMD when located upstream of an exon junction complex (EJC). Degradation of PTC-containing mRNAs requires the endonucleolytic activity of SMG6, a conserved NMD factor; nevertheless, the precise role for the EJC in NMD and how the SMG6 endonuclease is recruited to NMD targets have been unclear. Here we show that SMG6 interacts directly with the EJC via two conserved EJC-binding motifs (EBMs). We further show that the SMG6-EJC interaction is required for NMD. Our results reveal an unprecedented role for the EJC in recruiting the SMG6 endonuclease to NMD targets. More generally, our findings identify the EBM as a protein motif present in a handful of proteins, and suggest that EJCs establish multiple and mutually exclusive interactions with various protein partners, providing a plausible explanation for the myriad functions performed by this complex in post-transcriptional mRNA regulation.

journal_name

Genes Dev

journal_title

Genes & development

authors

Kashima I,Jonas S,Jayachandran U,Buchwald G,Conti E,Lupas AN,Izaurralde E

doi

10.1101/gad.604610

subject

Has Abstract

pub_date

2010-11-01 00:00:00

pages

2440-50

issue

21

eissn

0890-9369

issn

1549-5477

pii

gad.604610

journal_volume

24

pub_type

杂志文章
  • Coregulation of anterior and posterior mesendodermal development by a hairy-related transcriptional repressor.

    abstract::During embryonic development in vertebrates, the endoderm becomes patterned along the anteroposterior axis to produce distinct derivatives. How this regulation is controlled is not well understood. We report that the zebrafish hairy/enhancer of split [E(spl)]-related gene her5 plays a critical role in this process. At...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:

    authors: Bally-Cuif L,Goutel C,Wassef M,Wurst W,Rosa F

    更新日期:2000-07-01 00:00:00

  • Lysine methylation within the globular domain of histone H3 by Dot1 is important for telomeric silencing and Sir protein association.

    abstract::The amino-terminal histone tails are subject to covalent post-translational modifications such as acetylation, methylation, and phosphorylation. In the histone code hypothesis, these exposed and unstructured histone tails are accessible to a repertoire of regulatory factors that specifically recognize the various modi...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1001502

    authors: Ng HH,Feng Q,Wang H,Erdjument-Bromage H,Tempst P,Zhang Y,Struhl K

    更新日期:2002-06-15 00:00:00

  • OBP100 binds remarkably degenerate octamer motifs through specific interactions with flanking sequences.

    abstract::We have used the 100-kD HeLa cell octamer-binding protein OBP100 as a model to study flexible DNA sequence recognition by promoter-binding proteins. OBP100 binds to the conserved octamer motif ATGCAAAT found in numerous promoters and additionally to two degenerate octamer motifs (sites I and II) within the SV40 enhanc...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.2.11.1400

    authors: Baumruker T,Sturm R,Herr W

    更新日期:1988-11-01 00:00:00

  • HAESA, an Arabidopsis leucine-rich repeat receptor kinase, controls floral organ abscission.

    abstract::Abcission, the natural shedding of leaves, flowers and fruits, is a fundamental component of plant development. Abscission is a highly regulated process that occurs at distinct zones of cells that undergo enlargement and subsequent separation. Although some components of abscission, including accumulation of the hormo...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:

    authors: Jinn TL,Stone JM,Walker JC

    更新日期:2000-01-01 00:00:00

  • SIX2 and SIX3 coordinately regulate functional maturity and fate of human pancreatic β cells.

    abstract::The physiological functions of many vital tissues and organs continue to mature after birth, but the genetic mechanisms governing this postnatal maturation remain an unsolved mystery. Human pancreatic β cells produce and secrete insulin in response to physiological cues like glucose, and these hallmark functions impro...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.342378.120

    authors: Bevacqua RJ,Lam JY,Peiris H,Whitener RL,Kim S,Gu X,Friedlander MSH,Kim SK

    更新日期:2021-01-14 00:00:00

  • MT1-MMP regulates the PI3Kδ·Mi-2/NuRD-dependent control of macrophage immune function.

    abstract::Macrophages play critical roles in events ranging from host defense to obesity and cancer, where they infiltrate affected tissues and orchestrate immune responses in tandem with the remodeling of the extracellular matrix (ECM). Despite the dual roles played by macrophages in inflammation, the functions of macrophage-d...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.178749.111

    authors: Shimizu-Hirota R,Xiong W,Baxter BT,Kunkel SL,Maillard I,Chen XW,Sabeh F,Liu R,Li XY,Weiss SJ

    更新日期:2012-02-15 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

    doi:10.1101/gad.13.7.798

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

    更新日期:1999-04-01 00:00:00

  • A Drosophila rRNA gene located in euchromatin is active in transcription and nucleolus formation.

    abstract::P-element transformants of a single rRNA gene (rDNA) were used to investigate the relationship between the organization of the nucleolus organizer (NO) and rDNA function in Drosophila melanogaster. In situ hybridization to rRNA in polytene nuclei of salivary glands demonstrated that an rRNA gene can be transcribed at ...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.2.12b.1745

    authors: Karpen GH,Schaefer JE,Laird CD

    更新日期:1988-12-01 00:00:00

  • Localization of RecA-like recombination proteins on chromosomes of the lily at various meiotic stages.

    abstract::The Rad51 and Lim15 proteins of lily, which are homologs of the bacterial RecA protein, were found on chromosomes in various stages of meiotic prophase 1. The presence of both Rad51 and Lim15 proteins as discrete foci on leptotene and zygotene chromosomes and their colocalization suggest that meiotic recombination beg...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.9.8.925

    authors: Terasawa M,Shinohara A,Hotta Y,Ogawa H,Ogawa T

    更新日期:1995-04-15 00:00:00

  • Wild-type and cancer-related p53 proteins are preferentially degraded by MDM2 as dimers rather than tetramers.

    abstract::The p53 tumor suppressor protein is the most well studied as a regulator of transcription in the nucleus, where it exists primarily as a tetramer. However, there are other oligomeric states of p53 that are relevant to its regulation and activities. In unstressed cells, p53 is normally held in check by MDM2 that target...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.304071.117

    authors: Katz C,Low-Calle AM,Choe JH,Laptenko O,Tong D,Joseph-Chowdhury JN,Garofalo F,Zhu Y,Friedler A,Prives C

    更新日期:2018-03-01 00:00:00

  • SCAMP4 enhances the senescent cell secretome.

    abstract::The senescence-associated secretory phenotype (SASP) is a major trait of senescent cells, but the molecular regulators of SASP factor secretion are poorly understood. Mass spectrometry analysis revealed that secretory carrier membrane protein 4 (SCAMP4) levels were strikingly elevated on the surface of senescent cells...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.313270.118

    authors: Kim KM,Noh JH,Bodogai M,Martindale JL,Pandey PR,Yang X,Biragyn A,Abdelmohsen K,Gorospe M

    更新日期:2018-07-01 00:00:00

  • The helix-loop-helix protein Id-2 enhances cell proliferation and binds to the retinoblastoma protein.

    abstract::Cell growth and differentiation are usually antagonistic. Proteins of the basic helix-loop-helix (bHLH) family bind DNA and play important roles in the differentiation of specific cell types. Id proteins heterodimerize with bHLH transcription factors, blocking their activation of lineage-specific gene expression and t...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.8.11.1270

    authors: Iavarone A,Garg P,Lasorella A,Hsu J,Israel MA

    更新日期:1994-06-01 00:00:00

  • Inhibition of early apoptotic events by Akt/PKB is dependent on the first committed step of glycolysis and mitochondrial hexokinase.

    abstract::The serine/threonine kinase Akt/PKB is a major downstream effector of growth factor-mediated cell survival. Activated Akt, like Bcl-2 and Bcl-xL, prevents closure of a PT pore component, the voltage-dependent anion channel (VDAC); intracellular acidification; mitochondrial hyperpolarization; and the decline in oxidati...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.889901

    authors: Gottlob K,Majewski N,Kennedy S,Kandel E,Robey RB,Hay N

    更新日期:2001-06-01 00:00:00

  • Frequent provirus insertional mutagenesis of Notch1 in thymomas of MMTVD/myc transgenic mice suggests a collaboration of c-myc and Notch1 for oncogenesis.

    abstract::The MMTVD/myc transgenic mice spontaneously develop oligoclonal CD4+CD8+ T-cell tumors. We used provirus insertional mutagenesis in these mice to identify putative collaborators of c-myc. We found that Notch1 was mutated in a high proportion (52%) of these tumors. Proviruses were inserted upstream of the exon coding f...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.10.15.1930

    authors: Girard L,Hanna Z,Beaulieu N,Hoemann CD,Simard C,Kozak CA,Jolicoeur P

    更新日期:1996-08-01 00:00:00

  • Methylation of RUNX1 by PRMT1 abrogates SIN3A binding and potentiates its transcriptional activity.

    abstract::RUNX1/AML1 is required for the development of definitive hematopoiesis, and its activity is altered by mutations, deletions, and chromosome translocations in human acute leukemia. RUNX1 function can be regulated by post-translational modifications and protein-protein interactions. We show that RUNX1 is arginine-methyl...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1632608

    authors: Zhao X,Jankovic V,Gural A,Huang G,Pardanani A,Menendez S,Zhang J,Dunne R,Xiao A,Erdjument-Bromage H,Allis CD,Tempst P,Nimer SD

    更新日期:2008-03-01 00:00:00

  • Inhibition of viral gene expression by the catalytic RNA subunit of RNase P from Escherichia coli.

    abstract::The catalytic RNA subunit (M1 RNA) of RNase P from Escherichia coli has been converted to an endoribonuclease that specifically cleaves the mRNA that encodes thymidine kinase (TK) of herpes simplex virus 1 (HSV-1). Covalent attachment to the 3' end of M1 RNA of a sequence complementary to TK mRNA results in very effic...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.9.4.471

    authors: Liu F,Altman S

    更新日期:1995-02-15 00:00:00

  • The stringent response in Myxococcus xanthus is regulated by SocE and the CsgA C-signaling protein.

    abstract::Myxococcus xanthus fruiting body development is induced by amino acid limitation. The decision to grow or develop is established by the RelA-dependent stringent response and A-signaling. We identified two new members of this regulatory hierarchy, socE and the C-signaling gene csgA. SocE depletion arrests growth and in...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:

    authors: Crawford EW Jr,Shimkets LJ

    更新日期:2000-02-15 00:00:00

  • Axin-mediated CKI phosphorylation of beta-catenin at Ser 45: a molecular switch for the Wnt pathway.

    abstract::The Wnt pathway controls numerous developmental processes via the beta-catenin-TCF/LEF transcription complex. Deregulation of the pathway results in the aberrant accumulation of beta-catenin in the nucleus, often leading to cancer. Normally, cytoplasmic beta-catenin associates with APC and axin and is continuously pho...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.230302

    authors: Amit S,Hatzubai A,Birman Y,Andersen JS,Ben-Shushan E,Mann M,Ben-Neriah Y,Alkalay I

    更新日期:2002-05-01 00:00:00

  • A YAP/TAZ-induced feedback mechanism regulates Hippo pathway homeostasis.

    abstract::YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif) are major downstream effectors of the Hippo pathway that influences tissue homeostasis, organ size, and cancer development. Aberrant hyperactivation of YAP/TAZ causes tissue overgrowth and tumorigenesis, whereas their inactivatio...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.262816.115

    authors: Moroishi T,Park HW,Qin B,Chen Q,Meng Z,Plouffe SW,Taniguchi K,Yu FX,Karin M,Pan D,Guan KL

    更新日期:2015-06-15 00:00:00

  • Dosage compensation plans: protein aggregation provides additional insurance against aneuploidy.

    abstract::Gene dosage alterations caused by aneuploidy are a common feature of most cancers yet pose severe proteotoxic challenges. Therefore, cells have evolved various dosage compensation mechanisms to limit the damage caused by the ensuing protein level imbalances. For instance, for heteromeric protein complexes, excess nons...

    journal_title:Genes & development

    pub_type: 评论

    doi:10.1101/gad.329383.119

    authors: Samant RS,Masto VB,Frydman J

    更新日期:2019-08-01 00:00:00

  • Cotranscriptional recruitment of the dosage compensation complex to X-linked target genes.

    abstract::Dosage compensation is a process required to balance the expression of X-linked genes between males and females. In Drosophila this is achieved by targeting the dosage compensation complex or the male-specific lethal (MSL) complex to the male X chromosome. In order to study the mechanism of targeting, we have studied ...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.430807

    authors: Kind J,Akhtar A

    更新日期:2007-08-15 00:00:00

  • The Drosophila abrupt gene encodes a BTB-zinc finger regulatory protein that controls the specificity of neuromuscular connections.

    abstract::Motor axons make synaptic connections with specific muscles, and this specificity unfolds during development as motoneuron growth cones make specific pathway choices and ultimately recognize and synapse on their specific muscle targets. The Drosophila clueless mutation was identified previously in a genetic screen for...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.9.23.2936

    authors: Hu S,Fambrough D,Atashi JR,Goodman CS,Crews ST

    更新日期:1995-12-01 00:00:00

  • Circular forms of developmentally excised DNA in Euplotes crassus have a heteroduplex junction.

    abstract::Extensive DNA elimination via a DNA breakage and rejoining process occurs during macronuclear development in the hypotrich ciliate Euplotes crassus. The excision process involves the removal of short, unique segments of DNA (internal eliminated sequences; IESs) and at least two highly repetitive families of transposon...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.7.1.84

    authors: Klobutcher LA,Turner LR,LaPlante J

    更新日期:1993-01-01 00:00:00

  • A genome-wide RNAi screen identifies multiple RSK-dependent regulators of cell migration.

    abstract::To define the functional pathways regulating epithelial cell migration, we performed a genome-wide RNAi screen using 55,000 pooled lentiviral shRNAs targeting ∼11,000 genes, selecting for transduced cells with increased motility. A stringent validation protocol generated a set of 31 genes representing diverse pathways...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1989110

    authors: Smolen GA,Zhang J,Zubrowski MJ,Edelman EJ,Luo B,Yu M,Ng LW,Scherber CM,Schott BJ,Ramaswamy S,Irimia D,Root DE,Haber DA

    更新日期:2010-12-01 00:00:00

  • The Rho-linked mental retardation protein oligophrenin-1 controls synapse maturation and plasticity by stabilizing AMPA receptors.

    abstract::Oligophrenin-1 (OPHN1) encodes a Rho-GTPase-activating protein (Rho-GAP) whose loss of function has been associated with X-linked mental retardation (MR). The pathophysiological role of OPHN1, however, remains poorly understood. Here we show that OPHN1 through its Rho-GAP activity plays a critical role in the activity...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1783809

    authors: Nadif Kasri N,Nakano-Kobayashi A,Malinow R,Li B,Van Aelst L

    更新日期:2009-06-01 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

    doi:10.1101/gad.237628.114

    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

  • Genome-wide identification of microRNA targets in human ES cells reveals a role for miR-302 in modulating BMP response.

    abstract::MicroRNAs are important regulators in many cellular processes, including stem cell self-renewal. Recent studies demonstrated their function as pluripotency factors with the capacity for somatic cell reprogramming. However, their role in human embryonic stem (ES) cells (hESCs) remains poorly understood, partially due t...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.17221311

    authors: Lipchina I,Elkabetz Y,Hafner M,Sheridan R,Mihailovic A,Tuschl T,Sander C,Studer L,Betel D

    更新日期:2011-10-15 00:00:00

  • Heritable activity: a prion that propagates by covalent autoactivation.

    abstract::Known prions (infectious proteins) are self-propagating amyloids or conformationally altered proteins, but in theory an enzyme necessary for its own activation could also be a prion (or a gene composed of protein). We show that yeast protease B is such a prion, called [beta].[beta] is infectious, reversibly curable, a...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1115803

    authors: Roberts BT,Wickner RB

    更新日期:2003-09-01 00:00:00

  • A subtilisin-like serine protease involved in the regulation of stomatal density and distribution in Arabidopsis thaliana.

    abstract::Stomata are specialized cellular structures in the epidermis of aerial plant organs that control gas exchange (H(2)O release and CO(2) uptake) between leaves and the atmosphere by modulating the aperture of a pore flanked by two guard cells. Stomata are nonrandomly distributed, and their density is controlled by endog...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:

    authors: Berger D,Altmann T

    更新日期:2000-05-01 00:00:00

  • Chromatin and nucleosome dynamics in DNA damage and repair.

    abstract::Chromatin is organized into higher-order structures that form subcompartments in interphase nuclei. Different categories of specialized enzymes act on chromatin and regulate its compaction and biophysical characteristics in response to physiological conditions. We present an overview of the function of chromatin struc...

    journal_title:Genes & development

    pub_type: 杂志文章,评审

    doi:10.1101/gad.307702.117

    authors: Hauer MH,Gasser SM

    更新日期:2017-11-15 00:00:00