BTG2 Bridges PABPC1 RNA-Binding Domains and CAF1 Deadenylase to Control Cell Proliferation
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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. -
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. -
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. -
Mutation in a Primate-Conserved Retrotransposon Reveals a Noncoding RNA As a Mediator of Infantile Encephalopathy
Mutation in a primate-conserved retrotransposon reveals a noncoding RNA as a mediator of infantile encephalopathy François Cartaulta,b,1, Patrick Muniera, Edgar Benkoc, Isabelle Desguerred, Sylvain Haneinb, Nathalie Boddaerte, Simonetta Bandierab, Jeanine Vellayoudoma, Pascale Krejbich-Trototf, Marc Bintnerg, Jean-Jacques Hoarauf, Muriel Girardb, Emmanuelle Géninh, Pascale de Lonlayb, Alain Fourmaintrauxa,i, Magali Navillej, Diana Rodriguezk, Josué Feingoldb, Michel Renouili, Arnold Munnichb,l, Eric Westhofm, Michael Fählingc,2, Stanislas Lyonnetb,l,2, and Alexandra Henrion-Caudeb,1 aDépartement de Génétique and fGroupe de Recherche Immunopathologies et Maladies Infectieuses, Université de La Réunion, Centre Hospitalier Régional de La Réunion, 97405 Saint-Denis, La Réunion, France; bInstitut National de la Santé et de la Recherche Médicale (INSERM) U781 and Imagine Foundation, Hôpital Necker-Enfants Malades, Université Paris Descartes, 75015 Paris, France; cInstitut für Vegetative Physiologie, Charité-Universitätsmedizin Berlin, D-10115 Berlin, Germany; dDépartement de Neurologie Pédiatrique, eDépartement de Radio-Pédiatrie and INSERM Unité Mixte de Recherche (UMR)-1000, and lDépartement de Génétique, Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris, 75015 Paris, France; gDépartement de Neuroradiologie and iDépartement de Pédiatrie, Centre de Maladies Neuromusculaires et Neurologiques Rares, Centre Hospitalier Régional de La Réunion, 97448 Saint-Pierre, La Réunion, France; hINSERM U946, Fondation Jean Dausset, Centre -
(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. -
Regulation of Local Translation, Synaptic Plasticity, and Cognitive Function by CNOT7
University of Massachusetts Medical School eScholarship@UMMS GSBS Dissertations and Theses Graduate School of Biomedical Sciences 2017-07-31 Regulation of Local Translation, Synaptic Plasticity, and Cognitive Function by CNOT7 Rhonda L. McFleder University of Massachusetts Medical School Let us know how access to this document benefits ou.y Follow this and additional works at: https://escholarship.umassmed.edu/gsbs_diss Part of the Biochemistry Commons, and the Molecular and Cellular Neuroscience Commons Repository Citation McFleder RL. (2017). Regulation of Local Translation, Synaptic Plasticity, and Cognitive Function by CNOT7. GSBS Dissertations and Theses. https://doi.org/10.13028/M2KM3R. Retrieved from https://escholarship.umassmed.edu/gsbs_diss/915 This material is brought to you by eScholarship@UMMS. It has been accepted for inclusion in GSBS Dissertations and Theses by an authorized administrator of eScholarship@UMMS. For more information, please contact [email protected]. REGULATION OF LOCAL TRANSLATION, SYNAPTIC PLASTICITY, AND COGNITIVE FUNCTION BY CNOT7 A Dissertation Presented By Rhonda Leah McFleder Submitted to the Faculty of the University of Massachusetts Graduate School of Biomedical Sciences, Worcester in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY July 31, 2017 Program in Molecular Medicine iii ACKNOWLEDGEMENTS This work would not have been made possible without the leadership and guidance I received from my mentor, Dr. Joel Richter. I was warned before joining Joel’s lab that it would be “intense”, however I accepted the challenge and feel I am stronger person and scientist because of it. Joel helped me grow a backbone, which not only assisted me in working with him, but also gave me the confidence to pursue things I am passionate about both in science and everyday life. -
Defining the Caprin-1 Interactome in Unstressed and Stressed Conditions
bioRxiv preprint doi: https://doi.org/10.1101/2021.01.06.425453; this version posted January 7, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Defining the Caprin-1 interactome in unstressed and stressed conditions Lucas Vu1+, Asmita Ghosh2,3+, Chelsea Tran1,4, Walters Aji Tebung2,3, Hadjara Sidibé2,3, Krystine Garcia-Mansfield5, Victoria David-Dirgo5, Ritin Sharma5, Patrick Pirrotte5, Robert Bowser1, and Christine Vande Velde2,3 * 1 Department of Neurobiology, Barrow Neurological Institute, Phoenix, AZ, USA 2 Department of Neurosciences, Université de Montréal, Montreal, QC, Canada 3 CHUM Research Center, Montréal, QC, Canada 4 School of Life Sciences, Arizona State University, Tempe, AZ, USA 5 Collaborative Center for Translational Mass Spectrometry, Translational Genomics Research Institute, Phoenix, AZ, USA + These authors contributed equally to this work (co-first authors) * Corresponding Author Keywords: Caprin-1, Stress granules, Cytoplasmic inclusions, Proteomics, Mass spectrometry, RNA binding proteins, Amyotrophic lateral sclerosis, Protein-protein interactions, cytoplasmic granules Corresponding author: Christine Vande Velde, Ph.D. Department of Neurosciences, Université de Montréal CRCHUM-Tour Viger 900, rue Saint-Denis, R09.474 Montreal, QC, CANADA H2X 0A9 Email: [email protected] Phone: 514-890-8000 poste 28832 Fax: 514-412-7936 ORCID: orcid.org/0000-0001-5926-1529 1 bioRxiv preprint doi: https://doi.org/10.1101/2021.01.06.425453; this version posted January 7, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. -
University of Dundee the Mtor Regulated RNA-Binding Protein
University of Dundee The mTOR regulated RNA-binding protein LARP1 requires PABPC1 for guided mRNA interaction Smith, Ewan M.; Benbahouche, Nour El Houda; Morris, Katherine; Wilczynska, Ania; Gillen, Sarah; Schmidt, Tobias Published in: Nucleic Acids Research DOI: 10.1093/nar/gkaa1189 Publication date: 2021 Licence: CC BY Document Version Publisher's PDF, also known as Version of record Link to publication in Discovery Research Portal Citation for published version (APA): Smith, E. M., Benbahouche, N. E. H., Morris, K., Wilczynska, A., Gillen, S., Schmidt, T., Meijer, H. A., Jukes- Jones, R., Cain, K., Jones, C., Stoneley, M., Waldron, J. A., Bell, C., Fonseca, B. D., Blagden, S., Willis, A. E., & Bushell, M. (2021). The mTOR regulated RNA-binding protein LARP1 requires PABPC1 for guided mRNA interaction. Nucleic Acids Research, 49(1), 458-478. https://doi.org/10.1093/nar/gkaa1189 General rights Copyright and moral rights for the publications made accessible in Discovery Research Portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from Discovery Research Portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain. • You may freely distribute the URL identifying the publication in the public portal. Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. -
Winners Sorted by Institute-Center
FARE2020WINNERS Sorted By Institute Ji Chen Postdoctoral Fellow CC Neuroscience - General Toward a Wearable Pediatric Robotic Knee Exoskeleton for Real World Overground Gait Rehabilitation in Ambulatory Individuals Crouch gait, or excessive knee flexion, is a debilitating gait pathology in children with cerebral palsy (CP). Surgery, bracing and therapy provide only short term correction of crouch and more sustainable solutions remain a significant challenge in children with CP. One major hurdle is achieving the required dosage and intensity of gait training necessary to produce meaningful long term improvements in walking ability. Rather than replace lost or absent function, gait training in CP population aims to improve the participant’s baseline walking pattern by encouraging longer bouts of training and exercise, which is different than in those with paralysis. Wearable robotic exoskeletons, as a potential strategy, can assist individuals with CP to gradually regain knee extension over time and help maintain it for longer periods through intense task-specific gait training. We previously tested our initial prototype which produced significant improvement in knee extension comparable in magnitude to reported results from orthopedic surgery. Children continued to exert voluntary knee extensor muscle when walking with the exoskeleton which indicated the device was assisting but not controlling their gait. These positive initial results motivated us to design second prototype to expand the user population, and to enable its effective use outside of the laboratory environment. The current version has individualized control capability and device portability for home use as it implemented a multi-layered closed loop control system and a microcontroller based data acquisition system.