Autoregulation of TDP-43 mRNA levels involves interplay between transcription, splicing, and alternative polyA site selection.

Abstract:

:TDP-43 is a critical RNA-binding factor associated with pre-mRNA splicing in mammals. Its expression is tightly autoregulated, with loss of this regulation implicated in human neuropathology. We demonstrate that TDP-43 overexpression in humans and mice activates a 3' untranslated region (UTR) intron, resulting in excision of the proximal polyA site (PAS) pA(1). This activates a cryptic PAS that prevents TDP-43 expression through a nuclear retention mechanism. Superimposed on this process, overexpression of TDP-43 blocks recognition of pA(1) by competing with CstF-64 for PAS binding. Overall, we uncover complex interplay between transcription, splicing, and 3' end processing to effect autoregulation of TDP-43.

journal_name

Genes Dev

journal_title

Genes & development

authors

Avendaño-Vázquez SE,Dhir A,Bembich S,Buratti E,Proudfoot N,Baralle FE

doi

10.1101/gad.194829.112

subject

Has Abstract

pub_date

2012-08-01 00:00:00

pages

1679-84

issue

15

eissn

0890-9369

issn

1549-5477

pii

26/15/1679

journal_volume

26

pub_type

杂志文章
  • A variant limb deformity transcript expressed in the embryonic mouse limb defines a novel formin.

    abstract::The formins constitute a set of protein isoforms encoded by the alternatively spliced transcripts arising from the limb deformity (ld) locus of the mouse. Mutations in this locus disrupt formation of the anteroposterior axis of the embryonic limb. Although ld transcripts are widely expressed during embryogenesis, we h...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.6.1.29

    authors: Jackson-Grusby L,Kuo A,Leder P

    更新日期:1992-01-01 00:00:00

  • Overcoming inhibition in the spindle checkpoint.

    abstract::Spindle checkpoint silencing is a critical step during mitosis that initiates chromosome segregation, yet surprisingly little is known about its mechanism. Protein phosphatase I (PP1) was shown recently to be a key player in this process, and in this issue of Genes & Deverlopment, Akiyoshi and colleagues (pp. 2887-289...

    journal_title:Genes & development

    pub_type: 评论,杂志文章,评审

    doi:10.1101/gad.1882109

    authors: Vanoosthuyse V,Hardwick KG

    更新日期:2009-12-15 00:00:00

  • Hematopoietic development of embryonic stem cells in vitro: cytokine and receptor gene expression.

    abstract::A novel system to study early hematopoietic development is described. This report documents the in vitro capacity of murine embryonic stem (ES) cells to differentiate into hematopoietic precursors of most, if not all, of the colony-forming cells found in normal bone marrow. This system is used to correlate the genetic...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.5.5.728

    authors: Schmitt RM,Bruyns E,Snodgrass HR

    更新日期:1991-05-01 00:00:00

  • canoe encodes a novel protein containing a GLGF/DHR motif and functions with Notch and scabrous in common developmental pathways in Drosophila.

    abstract::The canoemisty1 (cnomis1) mutation was isolated by virtue of its severe rough eye phenotype from approximately 500 fly lines, each harboring a single autosomal insertion of a P element (Bm delta w). Excision of the P element generated a lethal, null allele, cnomis10, together with many revertants with normal eye morph...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.9.5.612

    authors: Miyamoto H,Nihonmatsu I,Kondo S,Ueda R,Togashi S,Hirata K,Ikegami Y,Yamamoto D

    更新日期:1995-03-01 00:00:00

  • ELAV tumor antigen, Hel-N1, increases translation of neurofilament M mRNA and induces formation of neurites in human teratocarcinoma cells.

    abstract::Human ELAV proteins are implicated in cell growth and differentiation via regulation of mRNA expression in the cytoplasm. In human embryonic teratocarcinoma (hNT2) cells transfected with the human neuronal ELAV-like protein, Hel-N1, neurites formed, yet cells were not terminally differentiated. Cells in which neurite ...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.13.4.449

    authors: Antic D,Lu N,Keene JD

    更新日期:1999-02-15 00:00:00

  • Different upstream transcriptional activators have distinct coactivator requirements.

    abstract::Activated transcription by RNA polymerase II (Pol II) requires coactivators, one of which is the SRB/mediator. Whereas Srb4, an essential subunit of the SRB/mediator, is broadly required for Pol II transcription in yeast, we have shown that it is dispensable for the transcriptional activation of some genes. Here, we s...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.13.22.2934

    authors: Lee DK,Kim S,Lis JT

    更新日期:1999-11-15 00:00:00

  • Centriole distal appendages promote membrane docking, leading to cilia initiation.

    abstract::The distal appendages (DAPs) of centrioles have been proposed to anchor cilia to the plasma membrane, but their molecular composition, assembly, and exact function in ciliogenesis remain poorly understood. Using quantitative centrosome proteomics and superresolution microscopy, we identified five DAP components, inclu...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.207043.112

    authors: Tanos BE,Yang HJ,Soni R,Wang WJ,Macaluso FP,Asara JM,Tsou MF

    更新日期:2013-01-15 00:00:00

  • Histone chaperone ASF1 cooperates with the Brahma chromatin-remodelling machinery.

    abstract::De novo chromatin assembly into regularly spaced nucleosomal arrays is essential for eukaryotic genome maintenance and inheritance. The Anti-Silencing Function 1 protein (ASF1) has been shown to be a histone chaperone, participating in DNA-replication-coupled nucleosome assembly. We show that mutations in the Drosophi...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.231202

    authors: Moshkin YM,Armstrong JA,Maeda RK,Tamkun JW,Verrijzer P,Kennison JA,Karch F

    更新日期:2002-10-15 00:00:00

  • TFIIIC determines RNA polymerase III specificity at the TATA-containing yeast U6 promoter.

    abstract::The gene encoding yeast U6 snRNA that is transcribed by RNA polymerase III (Pol III) contains both a TATA box upstream of the transcription start site and a downstream binding site for the factor TFIIIC. This juxtaposition of elements typical of both Pol II- and Pol III-transcribed genes raises the question of how pol...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.9.7.832

    authors: Roberts S,Colbert T,Hahn S

    更新日期:1995-04-01 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

  • Drosophila IRBP/Ku p70 corresponds to the mutagen-sensitive mus309 gene and is involved in P-element excision in vivo.

    abstract::The P family of transposable elements in Drosophila transpose by a cut-and-paste mechanism involving double-strand gap repair. We report here that a Drosophila mutagen-sensitive mutant, mus3O9, contains a mutation in IRBP (inverted repeat binding protein), the Drosophila homolog of the mammalian Ku p70 gene. We show t...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.10.8.921

    authors: Beall EL,Rio DC

    更新日期:1996-04-15 00:00:00

  • Fission yeast genes that confer resistance to staurosporine encode an AP-1-like transcription factor and a protein kinase related to the mammalian ERK1/MAP2 and budding yeast FUS3 and KSS1 kinases.

    abstract::Staurosporine, a potent inhibitor of protein kinase C, arrests fission yeast cell elongation specifically at a stage immediately after cell division. We isolated two genes, which, when carried on multicopy plasmids, confer drug resistance in fission yeast. One, spk1+, encodes a protein kinase highly similar (54% ident...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.5.1.60

    authors: Toda T,Shimanuki M,Yanagida M

    更新日期:1991-01-01 00:00:00

  • Malignant melanoma: genetics and therapeutics in the genomic era.

    abstract::Cell for cell, probably no human cancer is as aggressive as melanoma. It is among a handful of cancers whose dimensions are reported in millimeters. Tumor thickness approaching 4 mm presents a high risk of metastasis, and a diagnosis of metastatic melanoma carries with it an abysmal median survival of 6-9 mo. What fea...

    journal_title:Genes & development

    pub_type: 杂志文章,评审

    doi:10.1101/gad.1437206

    authors: Chin L,Garraway LA,Fisher DE

    更新日期:2006-08-15 00:00:00

  • The Drosophila takeout gene is regulated by the somatic sex-determination pathway and affects male courtship behavior.

    abstract::The Drosophila somatic sex-determination regulatory pathway has been well studied, but little is known about the target genes that it ultimately controls. In a differential screen for sex-specific transcripts expressed in fly heads, we identified a highly male-enriched transcript encoding Takeout, a protein related to...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1010302

    authors: Dauwalder B,Tsujimoto S,Moss J,Mattox W

    更新日期:2002-11-15 00:00:00

  • Vein expression is induced by the EGF receptor pathway to provide a positive feedback loop in patterning the Drosophila embryonic ventral ectoderm.

    abstract::The presence of a single EGF receptor in Drosophila is contrasted by multiple ligands activating it. This work explores the role of two ligands, Spitz and Vein, in the embryonic ventral ectoderm. Spitz is a potent ligand, whereas Vein is an intrinsically weak activating ligand. We show that secreted Spitz emanating fr...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.13.2.158

    authors: Golembo M,Yarnitzky T,Volk T,Shilo BZ

    更新日期:1999-01-15 00:00:00

  • A single Hox locus in Drosophila produces functional microRNAs from opposite DNA strands.

    abstract::MicroRNAs (miRNAs) are approximately 22-nucleotide RNAs that are processed from characteristic precursor hairpins and pair to sites in messages of protein-coding genes to direct post-transcriptional repression. Here, we report that the miRNA iab-4 locus in the Drosophila Hox cluster is transcribed convergently from bo...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1613108

    authors: Stark A,Bushati N,Jan CH,Kheradpour P,Hodges E,Brennecke J,Bartel DP,Cohen SM,Kellis M

    更新日期:2008-01-01 00:00:00

  • Cell-cycle regulation of a human histone H2b gene is mediated by the H2b subtype-specific consensus element.

    abstract::Mammalian histone gene transcription is increased approximately fivefold during the transition from the G1 phase to the S phase of the cell cycle. In this study, we present a detailed in vivo analysis of the human histone H2b promoter, which establishes that transcriptional regulation of this gene is mediated by a sub...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.2.1.32

    authors: LaBella F,Sive HL,Roeder RG,Heintz N

    更新日期:1988-01-01 00:00:00

  • Identification of in vivo mRNA targets of GLD-1, a maxi-KH motif containing protein required for C. elegans germ cell development.

    abstract::Caenorhabditis elegans GLD-1, a KH motif containing RNA-binding protein of the GSG/STAR subfamily, controls diverse aspects of germ line development, suggesting that it may have multiple mRNA targets. We used an immunoprecipitation/subtractive hybridization/cloning strategy to identify 15 mRNAs that are putative targe...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.915901

    authors: Lee MH,Schedl T

    更新日期:2001-09-15 00:00:00

  • BR-dependent phosphorylation modulates PIF4 transcriptional activity and shapes diurnal hypocotyl growth.

    abstract::Signaling by the hormones brassinosteroid (BR) and gibberellin (GA) is critical to normal plant growth and development and is required for hypocotyl elongation in response to dark and elevated temperatures. Active BR signaling is essential for GA promotion of hypocotyl growth and suppresses the dwarf phenotype of GA m...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.243675.114

    authors: Bernardo-García S,de Lucas M,Martínez C,Espinosa-Ruiz A,Davière JM,Prat S

    更新日期:2014-08-01 00:00:00

  • Foxp1 regulation of neonatal vocalizations via cortical development.

    abstract::The molecular mechanisms driving brain development at risk in autism spectrum disorders (ASDs) remain mostly unknown. Previous studies have implicated the transcription factor FOXP1 in both brain development and ASD pathophysiology. However, the specific molecular pathways both upstream of and downstream from FOXP1 ar...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.305037.117

    authors: Usui N,Araujo DJ,Kulkarni A,Co M,Ellegood J,Harper M,Toriumi K,Lerch JP,Konopka G

    更新日期:2017-10-15 00:00:00

  • CXCR4 and Gab1 cooperate to control the development of migrating muscle progenitor cells.

    abstract::Long-range migrating progenitor cells generate hypaxial muscle, for instance the muscle of the limbs, hypoglossal cord, and diaphragm. We show here that migrating muscle progenitors express the chemokine receptor CXCR4. The corresponding ligand, SDF1, is expressed in limb and branchial arch mesenchyme; i.e., along the...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.346205

    authors: Vasyutina E,Stebler J,Brand-Saberi B,Schulz S,Raz E,Birchmeier C

    更新日期:2005-09-15 00:00:00

  • RNAi drives nonreciprocal translocations at eroding chromosome ends to establish telomere-free linear chromosomes.

    abstract::The identification of telomerase-negative HAATI (heterochromatin amplification-mediated and telomerase-independent) cells, in which telomeres are superseded by nontelomeric heterochromatin tracts, challenged the idea that canonical telomeres are essential for chromosome linearity and raised crucial questions as to how...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.311712.118

    authors: Begnis M,Apte MS,Masuda H,Jain D,Wheeler DL,Cooper JP

    更新日期:2018-04-01 00:00:00

  • Homozygosity for prion protein alleles encoding glutamine-171 renders sheep susceptible to natural scrapie.

    abstract::Natural scrapie has been viewed both as a recessive trait and as a contagious disease modulated by a host locus. To address this conundrum, we determined the structure of the sheep prion protein (PrP) gene, which contains three exons and extends over 20 kb of DNA. In the United States 86.4% of scrapie cases occur in S...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.8.8.959

    authors: Westaway D,Zuliani V,Cooper CM,Da Costa M,Neuman S,Jenny AL,Detwiler L,Prusiner SB

    更新日期:1994-04-15 00:00:00

  • Opposing effects of TIGAR- and RAC1-derived ROS on Wnt-driven proliferation in the mouse intestine.

    abstract::Reactive oxygen species (ROS) participate in numerous cell responses, including proliferation, DNA damage, and cell death. Based on these disparate activities, both promotion and inhibition of ROS have been proposed for cancer therapy. However, how the ROS response is determined is not clear. We examined the activitie...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.271130.115

    authors: Cheung EC,Lee P,Ceteci F,Nixon C,Blyth K,Sansom OJ,Vousden KH

    更新日期:2016-01-01 00:00:00

  • Sox2 is required for development of taste bud sensory cells.

    abstract::Sox2 is expressed in basal epithelial cells of the tongue, with high levels in taste bud placodes, fungiform papillae, and mature taste cells, and low levels in filiform papillae. High Sox2 expression appears to lie downstream from canonical Wnt signaling. In hypomorphic Sox2(EGFP/LP) embryos, placodes form but no mat...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1457106

    authors: Okubo T,Pevny LH,Hogan BL

    更新日期:2006-10-01 00:00:00

  • RecE/RecT and Redalpha/Redbeta initiate double-stranded break repair by specifically interacting with their respective partners.

    abstract::The initial steps of double-stranded break (DSB) repair by homologous recombination mediated by the 5'-3' exonuclease/annealing protein pairs, RecE/RecT and Redalpha/Redbeta, were analyzed. Recombination was RecA-independent and required the expression of both components of an orthologous pair, even when the need for ...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:

    authors: Muyrers JP,Zhang Y,Buchholz F,Stewart AF

    更新日期:2000-08-01 00:00:00

  • Hedgehog signaling and the retina: insights into the mechanisms controlling the proliferative properties of neural precursors.

    abstract::Hedgehog signaling has been linked to cell proliferation in a variety of systems; however, its effects on the cell cycle have not been closely studied. In the vertebrate retina, Hedgehog's effects are controversial, with some reports emphasizing increased proliferation and others pointing to a role in cell cycle exit....

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.391106

    authors: Locker M,Agathocleous M,Amato MA,Parain K,Harris WA,Perron M

    更新日期:2006-11-01 00:00:00

  • Protein phosphatase 4 mediates localization of the Miranda complex during Drosophila neuroblast asymmetric divisions.

    abstract::Asymmetric localization of cell fate determinants is a crucial step in neuroblast asymmetric divisions. Whereas several protein kinases have been shown to mediate this process, no protein phosphatase has so far been implicated. In a clonal screen of larval neuroblasts we identified the evolutionarily conserved Protein...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1723609

    authors: Sousa-Nunes R,Chia W,Somers WG

    更新日期:2009-02-01 00:00:00

  • A condensin-like dosage compensation complex acts at a distance to control expression throughout the genome.

    abstract::In many species, a dosage compensation complex (DCC) is targeted to X chromosomes of one sex to equalize levels of X-gene products between males (1X) and females (2X). Here we identify cis-acting regulatory elements that target the Caenorhabditis elegans X chromosome for repression by the DCC. The DCC binds to discret...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1751109

    authors: Jans J,Gladden JM,Ralston EJ,Pickle CS,Michel AH,Pferdehirt RR,Eisen MB,Meyer BJ

    更新日期:2009-03-01 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

    doi:10.1101/gad.8.14.1703

    authors: Tian M,Maniatis T

    更新日期:1994-07-15 00:00:00