Mutation in a Primate-Conserved Retrotransposon Reveals a Noncoding RNA As a Mediator of Infantile Encephalopathy
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A Study on Acute Myeloid Leukemias with Trisomy 8, 11, Or 13, Monosomy 7, Or Deletion 5Q
Leukemia (2005) 19, 1224–1228 & 2005 Nature Publishing Group All rights reserved 0887-6924/05 $30.00 www.nature.com/leu Genomic gains and losses influence expression levels of genes located within the affected regions: a study on acute myeloid leukemias with trisomy 8, 11, or 13, monosomy 7, or deletion 5q C Schoch1, A Kohlmann1, M Dugas1, W Kern1, W Hiddemann1, S Schnittger1 and T Haferlach1 1Laboratory for Leukemia Diagnostics, Department of Internal Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University, Munich, Germany We performed microarray analyses in AML with trisomies 8 aim of this study to investigate whether gains and losses on the (n ¼ 12), 11 (n ¼ 7), 13 (n ¼ 7), monosomy 7 (n ¼ 9), and deletion genomic level translate into altered genes expression also in 5q (n ¼ 7) as sole changes to investigate whether genomic gains and losses translate into altered expression levels of other areas of the genome in AML. genes located in the affected chromosomal regions. Controls were 104 AML with normal karyotype. In subgroups with trisomy, the median expression of genes located on gained Materials and methods chromosomes was higher, while in AML with monosomy 7 and deletion 5q the median expression of genes located in deleted Samples regions was lower. The 50 most differentially expressed genes, as compared to all other subtypes, were equally distributed Bone marrow samples of AML patients at diagnosis were over the genome in AML subgroups with trisomies. In contrast, 30 and 86% of the most differentially expressed genes analyzed: 12 cases with trisomy 8 (AML-TRI8), seven with characteristic for AML with 5q deletion and monosomy 7 are trisomy 11 (AML-TRI11), seven with trisomy 13 (AML-TRI13), located on chromosomes 5 or 7. -
The Landscape of Human Mutually Exclusive Splicing
bioRxiv preprint doi: https://doi.org/10.1101/133215; this version posted May 2, 2017. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-ND 4.0 International license. The landscape of human mutually exclusive splicing Klas Hatje1,2,#,*, Ramon O. Vidal2,*, Raza-Ur Rahman2, Dominic Simm1,3, Björn Hammesfahr1,$, Orr Shomroni2, Stefan Bonn2§ & Martin Kollmar1§ 1 Group of Systems Biology of Motor Proteins, Department of NMR-based Structural Biology, Max-Planck-Institute for Biophysical Chemistry, Göttingen, Germany 2 Group of Computational Systems Biology, German Center for Neurodegenerative Diseases, Göttingen, Germany 3 Theoretical Computer Science and Algorithmic Methods, Institute of Computer Science, Georg-August-University Göttingen, Germany § Corresponding authors # Current address: Roche Pharmaceutical Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland $ Current address: Research and Development - Data Management (RD-DM), KWS SAAT SE, Einbeck, Germany * These authors contributed equally E-mail addresses: KH: [email protected], RV: [email protected], RR: [email protected], DS: [email protected], BH: [email protected], OS: [email protected], SB: [email protected], MK: [email protected] - 1 - bioRxiv preprint doi: https://doi.org/10.1101/133215; this version posted May 2, 2017. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. -
BTG2 Bridges PABPC1 RNA-Binding Domains and CAF1 Deadenylase to Control Cell Proliferation
ARTICLE Received 21 May 2015 | Accepted 24 Jan 2016 | Published 25 Feb 2016 DOI: 10.1038/ncomms10811 OPEN BTG2 bridges PABPC1 RNA-binding domains and CAF1 deadenylase to control cell proliferation Benjamin Stupfler1,2,3,4, Catherine Birck1,2,3,4, Bertrand Se´raphin1,2,3,4 & Fabienne Mauxion1,2,3,4 While BTG2 plays an important role in cellular differentiation and cancer, its precise molecular function remains unclear. BTG2 interacts with CAF1 deadenylase through its APRO domain, a defining feature of BTG/Tob factors. Our previous experiments revealed that expression of BTG2 promoted mRNA poly(A) tail shortening through an undefined mechanism. Here we report that the APRO domain of BTG2 interacts directly with the first RRM domain of the poly(A)-binding protein PABPC1. Moreover, PABPC1 RRM and BTG2 APRO domains are sufficient to stimulate CAF1 deadenylase activity in vitro in the absence of other CCR4–NOT complex subunits. Our results unravel thus the mechanism by which BTG2 stimulates mRNA deadenylation, demonstrating its direct role in poly(A) tail length control. Importantly, we also show that the interaction of BTG2 with the first RRM domain of PABPC1 is required for BTG2 to control cell proliferation. 1 Institut de Ge´ne´tique et de Biologie Mole´culaire et Cellulaire, 67404 Illkirch, France. 2 Centre National de la Recherche Scientifique UMR7104, 67404 Illkirch, France. 3 Institut National de la Sante´ et de la Recherche Me´dicale U964, 67404 Illkirch, France. 4 Universite´ de Strasbourg, 67404 Illkirch, France. Correspondence and requests for materials should be addressed to B.Se. (email: [email protected]) or to F.M. -
Tob2 Phosphorylation Regulates Global Mrna Turnover to Reshape Transcriptome and Impact Cell Proliferation
Downloaded from rnajournal.cshlp.org on October 6, 2021 - Published by Cold Spring Harbor Laboratory Press Research Article (Revised) Tob2 phosphorylation regulates global mRNA turnover to reshape transcriptome and impact cell proliferation Chyi-Ying A. Chen1, Krista Strouz1, Kai-Lieh Huang1, 2, and Ann-Bin Shyu1, * 1Department of Biochemistry and Molecular Biology, McGovern Medical School The University of Texas Health Science Center at Houston, Houston, Texas 77030 Running Title: Tob2-promoted deadenylation reshapes transcriptome Keywords: mRNA turnover, deadenylation, transcriptome programming, PABP interaction, Ccr4-Not complex, phosphorylation 2Current Address: Department of Biochemistry and Molecular Biology, University of Texas Medical Branch at Galveston, Galveston, Texas 77550 *Corresponding author: Tel: (713) 500-6068; Fax: (713) 500-0652; E-mail address: Ann- [email protected]. Downloaded from rnajournal.cshlp.org on October 6, 2021 - Published by Cold Spring Harbor Laboratory Press Abstract Tob2, an anti-proliferative protein, promotes deadenylation through recruiting Caf1 deadenylase to the mRNA poly(A) tail by simultaneously interacting with both Caf1 and poly(A)-binding protein (PABP). Previously, we found that changes in Tob2 phosphorylation can alter its PABP- binding ability and deadenylation-promoting function. However, it remained unknown regarding the relevant kinase(s). Moreover, it was unclear whether Tob2 phosphorylation modulates the transcriptome and whether the phosphorylation is linked to Tob2’s anti-proliferative function. In this study, we found that c-Jun N-terminal kinase (JNK) increases phosphorylation of Tob2 at many Ser/Thr sites in the intrinsically disordered region (IDR) that contains two separate PABP- interacting PAM2 motifs. JNK-induced phosphorylation or phosphomimetic mutations at these sites weaken the Tob2-PABP interaction. -
Mechanism of Translation Regulation of BTG1 by Eif3 Master's Thesis
Mechanism of Translation Regulation of BTG1 by eIF3 Master’s Thesis Presented to The Faculty of the Graduate School of Arts and Sciences Brandeis University Department of Biology Amy S.Y. Lee, Advisor In Partial Fulfillment of the Requirements for the Degree Master of Science in Biology by Shih-Ming (Annie) Huang May 2019 Copyright by Shih-Ming (Annie) Huang © 2019 ACKNOWLEDGEMENT I would like to express my deepest gratitude to Dr. Amy S.Y. Lee for her continuous patience, support, encouragement, and guidance throughout this journey. I am very thankful for all the members of the Lee Lab for providing me with this caring and warm environment to complete my work. I would also like to thank Dr. James NuñeZ for collaborating with us on this project and helping us in any shape or form. iii ABSTRACT Mechanism of Translation Regulation of BTG1 by eIF3 A thesis presented to the Department of Biology Graduate School of Arts and Sciences Brandeis University Waltham, Massachusetts By Shih-Ming (Annie) Huang REDACTED iv TABLE OF CONTENTS REDACTED v LIST OF FIGURES REDACTED vi INTRODUCTION I. Gene Regulation All cells in our bodies contain the same genome, but distinct cell types express very different sets of genes. The sets of gene expressed under specific conditions determine what the cell can do, by controlling the proteins and functional RNAs the cell contains. The process of controlling which genes are expressed is known as gene regulation. Any step along the gene expression pathway can be controlled, from DNA transcription, translation of mRNAs into proteins, to post-translational modifications. -
Importance of CNOT8 Deadenylase Subunit in DNA Damage Responses Following Ionizing Radiation (IR)
Reports of Biochemistry & Molecular Biology Vol.9, No.1, July 2020 Original article www.RBMB.net Importance of CNOT8 Deadenylase Subunit in DNA Damage Responses Following Ionizing Radiation (IR) Samira Eskandarian1,2, Roger Grand2, Shiva Irani*1, Mohsen Saeedi3, Reza Mirfakhraie4 Abstract Background: The Ccr4-Not protein complex (CNOT complex) is a key regulator of gene expression in eukaryotic cells. Ccr4-Not Complex is composed of at least nine conserved subunits in mammalian cells with two main enzymatic activities. CNOT8 is a subunit of the complex with deadenylase activity that interacts transiently with the CNOT6 or CNOT6L subunits. Here, we focused on the role of the human CNOT8 subunit in the DNA damage response (DDR). Methods: Cell viability was assessed to measure ATP level using a Cell Titer-Glo Luminescence reagent up to 4 days’ post CNOT8 siRNA transfection. In addition, expression level of phosphorylated proteins in signalling pathways were detected by western blotting and immunofluorescence microscopy. CNOT8- depleted Hela cells post- 3 Gy ionizing radiation (IR) treatment were considered as a control. Results: Our results from cell viability assays indicated a significant reduction at 72-hour post CNOT8 siRNA transfection (p= 0.04). Western blot analysis showed slightly alteration in the phosphorylation of DNA damage response (DDR) proteins in CNOT8-depleted HeLa cells following treatment with ionizing radiation (IR). Increased foci formation of H2AX, RPA, 53BP1, and RAD51 foci was observed after IR in CNOT8-depleted cells compared to the control cells. Conclusions: We conclude that CNOT8 deadenylase subunit is involved in the cellular response to DNA damage. Keywords: CNOT complex, CNOT8, DNA damage response, SiRNA. -
Novel IQCE Variations Confirm Its Role in Postaxial Polydactyly and Cause
Novel IQCE variations confirm its role in postaxial polydactyly and cause ciliary defect phenotype in zebrafish Alejandro Estrada-Cuzcano, Christelle Etard, Clarisse Delvallée, Corinne Stoetzel, Elise Schaefer, Sophie Scheidecker, Véronique Geoffroy, Aline Schneider, Fouzia Studer, Francesca Mattioli, et al. To cite this version: Alejandro Estrada-Cuzcano, Christelle Etard, Clarisse Delvallée, Corinne Stoetzel, Elise Schaefer, et al.. Novel IQCE variations confirm its role in postaxial polydactyly and cause ciliary defect phenotype in zebrafish. Human Mutation, Wiley, 2019, 10.1002/humu.23924. hal-02304111 HAL Id: hal-02304111 https://hal.archives-ouvertes.fr/hal-02304111 Submitted on 2 Oct 2019 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Page 1 of 125 Human Mutation Novel IQCE variations confirm its role in postaxial polydactyly and cause ciliary defect phenotype in zebrafish. Alejandro Estrada-Cuzcano1*, Christelle Etard2*, Clarisse Delvallée1*, Corinne Stoetzel1, Elise Schaefer1,3, Sophie Scheidecker1,4, Véronique Geoffroy1, Aline Schneider1, Fouzia Studer5, Francesca Mattioli6, Kirsley Chennen1,7, Sabine Sigaudy8, Damien Plassard9, Olivier Poch7, Amélie Piton4,6, Uwe Strahle2, Jean Muller1,4* and Hélène Dollfus1,3,5* 1. Laboratoire de Génétique médicale, UMR_S INSERM U1112, IGMA, Faculté de Médecine FMTS, Université de Strasbourg, Strasbourg, France. -
A Metastasis Modifier Locus on Human Chromosome 8P in Uveal Melanoma Identified by Integrative Genomic Analysis Michaeld.Onken,Loria.Worley,Andj.Williamharbour
Human Cancer Biology A Metastasis Modifier Locus on Human Chromosome 8p in Uveal Melanoma Identified by Integrative Genomic Analysis MichaelD.Onken,LoriA.Worley,andJ.WilliamHarbour Abstract Purpose: To identify genes that modify metastatic risk in uveal melanoma, a type of cancer that is valuable for studying metastasis because of its remarkably consistent metastatic pattern and well-characterized gene expression signature associated with metastasis. Experimental Design: We analyzed 53 primary uveal melanomas by gene expression profiling, array-based comparative genomic hybridization, array-based global DNA methylation profiling, and single nucleotide polymorphism ^ based detection of loss of heterozygosity to identify modifiers of metastatic risk. A candidate gene, leucine zipper tumor suppressor-1 (LZTS1), was examined for its effect on proliferation, migration, and motility in cultured uveal melanoma cells. Results: In metastasizing primary uveal melanomas, deletion of chromosome 8p12-22 and DNA hypermethylation of the corresponding region of the retained hemizygous 8p allele were associated with more rapid metastasis. Among the 11genes located within the deleted region, LZTS1 was most strongly linked to rapid metastasis. LZTS1 was silenced in rapidly meta- stasizing and metastatic uveal melanomas but not in slowly metastasizing and nonmetastasizing uveal melanomas. Forced expression of LZTS1in metastasizing uveal melanoma cells inhibited their motility and invasion, whereas depletion of LZTS1increased their motility. Conclusions: We have described a metastatic modifier locus on chromosome 8pand identified LZTS1 as a potential metastasis suppressor within this region. This study shows the utility of integrative genomic methods for identifying modifiers of metastatic risk in human cancers and may suggest new therapeutic targets in metastasizing tumor cells. -
A Thirteen‑Gene Set Efficiently Predicts the Prognosis of Glioblastoma
MOLECULAR MEDICINE REPORTS 19: 1613-1621, 2019 A thirteen‑gene set efficiently predicts the prognosis of glioblastoma HUYIN YANG, LUHAO JIN and XIAOYANG SUN Department of Neurosurgery, Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China Received January 21, 2018; Accepted September 6, 2018 DOI: 10.3892/mmr.2019.9801 Abstract. Glioblastoma multiforme (GBM) is the most Introduction common type of brain cancer; it usually recurs and patients have a short survival time. The present study aimed to construct Glioblastoma multiforme (GBM) is the most common and the a gene expression classifier and to screen key genes associated most invasive subtype of brain cancer; it is characterized by with GBM prognosis. GSE7696 microarray data set included symptoms that include personality changes, headaches, nausea samples from 10 recurrent GBM tissues, 70 primary GBM and unconsciousness (1,2). GBM originates from normal brain tissues and 4 normal brain tissues. Seed genes were identi- cells or low-grade astrocytoma, and may be induced by genetic fied by the ‘survival’ package in R and subjected to pathway disorders and radiation exposure (3,4). Clinical techniques for enrichment analysis. Prognostic genes were selected from the the treatment of GBM include surgery combined with radia- seed genes using the ‘rbsurv’ package in R, unsupervised hier- tion therapy or chemotherapy; however, the survival benefit archical clustering, survival analysis and enrichment analysis. is limited to ~12-15 months, or even shorter if the disease Multivariate survival analysis was performed for the prog- recurs (4). nostic genes, and the GBM data set from The Cancer Genome Gene therapy is a novel strategy for treating cancers (5). -
Agricultural University of Athens
ΓΕΩΠΟΝΙΚΟ ΠΑΝΕΠΙΣΤΗΜΙΟ ΑΘΗΝΩΝ ΣΧΟΛΗ ΕΠΙΣΤΗΜΩΝ ΤΩΝ ΖΩΩΝ ΤΜΗΜΑ ΕΠΙΣΤΗΜΗΣ ΖΩΙΚΗΣ ΠΑΡΑΓΩΓΗΣ ΕΡΓΑΣΤΗΡΙΟ ΓΕΝΙΚΗΣ ΚΑΙ ΕΙΔΙΚΗΣ ΖΩΟΤΕΧΝΙΑΣ ΔΙΔΑΚΤΟΡΙΚΗ ΔΙΑΤΡΙΒΗ Εντοπισμός γονιδιωματικών περιοχών και δικτύων γονιδίων που επηρεάζουν παραγωγικές και αναπαραγωγικές ιδιότητες σε πληθυσμούς κρεοπαραγωγικών ορνιθίων ΕΙΡΗΝΗ Κ. ΤΑΡΣΑΝΗ ΕΠΙΒΛΕΠΩΝ ΚΑΘΗΓΗΤΗΣ: ΑΝΤΩΝΙΟΣ ΚΟΜΙΝΑΚΗΣ ΑΘΗΝΑ 2020 ΔΙΔΑΚΤΟΡΙΚΗ ΔΙΑΤΡΙΒΗ Εντοπισμός γονιδιωματικών περιοχών και δικτύων γονιδίων που επηρεάζουν παραγωγικές και αναπαραγωγικές ιδιότητες σε πληθυσμούς κρεοπαραγωγικών ορνιθίων Genome-wide association analysis and gene network analysis for (re)production traits in commercial broilers ΕΙΡΗΝΗ Κ. ΤΑΡΣΑΝΗ ΕΠΙΒΛΕΠΩΝ ΚΑΘΗΓΗΤΗΣ: ΑΝΤΩΝΙΟΣ ΚΟΜΙΝΑΚΗΣ Τριμελής Επιτροπή: Aντώνιος Κομινάκης (Αν. Καθ. ΓΠΑ) Ανδρέας Κράνης (Eρευν. B, Παν. Εδιμβούργου) Αριάδνη Χάγερ (Επ. Καθ. ΓΠΑ) Επταμελής εξεταστική επιτροπή: Aντώνιος Κομινάκης (Αν. Καθ. ΓΠΑ) Ανδρέας Κράνης (Eρευν. B, Παν. Εδιμβούργου) Αριάδνη Χάγερ (Επ. Καθ. ΓΠΑ) Πηνελόπη Μπεμπέλη (Καθ. ΓΠΑ) Δημήτριος Βλαχάκης (Επ. Καθ. ΓΠΑ) Ευάγγελος Ζωίδης (Επ.Καθ. ΓΠΑ) Γεώργιος Θεοδώρου (Επ.Καθ. ΓΠΑ) 2 Εντοπισμός γονιδιωματικών περιοχών και δικτύων γονιδίων που επηρεάζουν παραγωγικές και αναπαραγωγικές ιδιότητες σε πληθυσμούς κρεοπαραγωγικών ορνιθίων Περίληψη Σκοπός της παρούσας διδακτορικής διατριβής ήταν ο εντοπισμός γενετικών δεικτών και υποψηφίων γονιδίων που εμπλέκονται στο γενετικό έλεγχο δύο τυπικών πολυγονιδιακών ιδιοτήτων σε κρεοπαραγωγικά ορνίθια. Μία ιδιότητα σχετίζεται με την ανάπτυξη (σωματικό βάρος στις 35 ημέρες, ΣΒ) και η άλλη με την αναπαραγωγική -
(CCR4-Associated Factor 1) Family and Its Expression in Poplar
plants Article Genome-Wide and Comprehensive Analysis of the Multiple Stress-Related CAF1 (CCR4-Associated Factor 1) Family and Its Expression in Poplar Pu Wang, Lingling Li, Hui Wei, Weibo Sun, Peijun Zhou, Sheng Zhu, Dawei Li and Qiang Zhuge * Co-Innovation Center for Sustainable Forestry in Southern China, Key Laboratory of Forest Genetics & Biotechnology, Ministry of Education, College of Biology and the Environment, Nanjing Forestry University, Nanjing 210037, China; [email protected] (P.W.); [email protected] (L.L.); [email protected] (H.W.); [email protected] (W.S.); [email protected] (P.Z.); [email protected] (S.Z.); [email protected] (D.L.) * Correspondence: [email protected]; Fax: +86-25-85428701 Abstract: Poplar is one of the most widely used tree in afforestation projects. However, it is suscepti- ble to abiotic and biotic stress. CCR4-associated factor 1 (CAF1) is a major member of CCR4-NOT, and it is mainly involved in transcriptional regulation and mRNA degradation in eukaryotes. However, there are no studies on the molecular phylogeny and expression of the CAF1 gene in poplar. In this study, a total of 19 PtCAF1 genes were identified in the Populus trichocarpa genome. Phylogenetic analysis of the PtCAF1 gene family was performed with two closely related species (Arabidopsis thaliana and Oryza sativa) to investigate the evolution of the PtCAF1 gene. The tissue expression of the PtCAF1 gene showed that 19 PtCAF1 genes were present in different tissues of poplar. Additionally, Citation: Wang, P.; Li, L.; Wei, H.; the analysis of the expression of the PtCAF1 gene showed that the CAF1 family was up-regulated Sun, W.; Zhou, P.; Zhu, S.; Li, D.; to various degrees under biotic and abiotic stresses and participated in the poplar stress response. -
Centimorgan-Range One-Step Mapping of Fertility Traits Using Interspecific
Genetics: Published Articles Ahead of Print, published on May 4, 2007 as 10.1534/genetics.107.072157 1 Centimorgan-range one-step mapping of fertility traits using Interspecific Recombinant Congenic Mice David L'hôte*,‡, Catherine Serres†, Paul Laissue*, Ahmad Oulmouden‡, Claire Rogel- Gaillard** , Xavier Montagutelli§, Daniel Vaiman*,**,1. * Equipe 21, Génomique et Epigénétique des Pathologies Placentaires (GEPP), Unité INSERM 567 / UMR CNRS 8104 - Université Paris V IFR Alfred Jost, Faculté de Médecine, 75014 Paris, France † Université Paris Descartes, Faculté de Médecine de Cochin, Biologie de la Reproduction, 75014 Paris, France. ‡Unite de Genetique Moleculaire Animale, UMR 1061-INRA/Universite de Limoges, Limoges, France § Unite de Genetique des Mammiferes, Institut Pasteur, 75724 Paris cedex 15, France **Animal Genetics Department, INRA, France 2 Running title: Mapping of mouse fertility traits Key words: Mouse, QTL, Interspecific Recombinant Congenic Strain, Mus spretus, male fertility 1Corresponding author : Génomique et Epigénétique des Pathologies Placentaires (GEPP), Unité INSERM 567 / UMR CNRS 8104 - Université Paris V IFR Alfred Jost, Faculté de Médecine, 24 rue du faubourg Saint Jacques 75014 Paris, France. E-Mail : [email protected] 3 ABSTRACT In mammals, male fertility is a quantitative feature determined by numerous genes. Up to now, several wide chromosomal regions involved in fertility have been defined by genetic mapping approaches; unfortunately, the underlying genes are very difficult to identify. Here, fifty three strains of interspecific recombinant congenic mice (IRCS) bearing 1-2% SEG/Pas (Mus spretus) genomic fragments disseminated in a C57Bl/6J (Mus domesticus) background were used to systematically analyze male fertility parameters. One of the most prominent advantages of this model is the possibility of permanently coming back to living animals stable phenotypes.