How Nuclear Pore Complexes Assemble Marion Weberruss and Wolfram Antonin*
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
Novel Nesprin-1 Mutations Associated with Dilated
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by University of East Anglia digital repository Human Molecular Genetics, 2017, Vol. 0, No. 0 1–19 doi: 10.1093/hmg/ddx116 Advance Access Publication Date: 7 April 2017 Original Article ORIGINAL ARTICLE Novel nesprin-1 mutations associated with dilated cardiomyopathy cause nuclear envelope disruption and defects in myogenesis Can Zhou1,2,†, Chen Li1,2,†, Bin Zhou3,4, Huaqin Sun4,5, Victoria Koullourou1,6, Ian Holt7, Megan J. Puckelwartz8, Derek T. Warren1, Robert Hayward1, Ziyuan Lin4,5, Lin Zhang3,4, Glenn E. Morris7, Elizabeth M. McNally8, Sue Shackleton6, Li Rao2, Catherine M. Shanahan1,‡ and Qiuping Zhang1,*,‡ 1King’s College London British Heart Foundation Centre of Research Excellence, Cardiovascular Division, London SE5 9NU, UK, 2Department of Cardiology, West China Hospital of Sichuan University, Chengdu 610041, China, 3Laboratory of Molecular Translational Medicine, 4Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, 5SCU-CUHK Joint Laboratory for Reproductive Medicine, West China Second University Hospital, Sichuan University, Chengdu, 610041, China, 6Department of Molecular and Cell Biology, University of Leicester, Leicester LE1 9HN, UK, 7Wolfson Centre for Inherited Neuromuscular Disease, RJAH Orthopaedic Hospital, Oswestry SY10 7AG, UK and Institute for Science and Technology in Medicine, Keele University, ST5 5BG, UK and 8Center for Genetic Medicine, Northwestern University Feinberg -
Building the Interphase Nucleus: a Study on the Kinetics of 3D Chromosome Formation, Temporal Relation to Active Transcription, and the Role of Nuclear Rnas
University of Massachusetts Medical School eScholarship@UMMS GSBS Dissertations and Theses Graduate School of Biomedical Sciences 2020-07-28 Building the Interphase Nucleus: A study on the kinetics of 3D chromosome formation, temporal relation to active transcription, and the role of nuclear RNAs Kristin N. Abramo 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 Bioinformatics Commons, Cell Biology Commons, Computational Biology Commons, Genomics Commons, Laboratory and Basic Science Research Commons, Molecular Biology Commons, Molecular Genetics Commons, and the Systems Biology Commons Repository Citation Abramo KN. (2020). Building the Interphase Nucleus: A study on the kinetics of 3D chromosome formation, temporal relation to active transcription, and the role of nuclear RNAs. GSBS Dissertations and Theses. https://doi.org/10.13028/a9gd-gw44. Retrieved from https://escholarship.umassmed.edu/ gsbs_diss/1099 Creative Commons License This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License 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]. BUILDING THE INTERPHASE NUCLEUS: A STUDY ON THE KINETICS OF 3D CHROMOSOME FORMATION, TEMPORAL RELATION TO ACTIVE TRANSCRIPTION, AND THE ROLE OF NUCLEAR RNAS A Dissertation Presented By KRISTIN N. ABRAMO 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 PHILOSPOPHY July 28, 2020 Program in Systems Biology, Interdisciplinary Graduate Program BUILDING THE INTERPHASE NUCLEUS: A STUDY ON THE KINETICS OF 3D CHROMOSOME FORMATION, TEMPORAL RELATION TO ACTIVE TRANSCRIPTION, AND THE ROLE OF NUCLEAR RNAS A Dissertation Presented By KRISTIN N. -
Biogenesis of Nuclear Bodies
Downloaded from http://cshperspectives.cshlp.org/ on September 30, 2021 - Published by Cold Spring Harbor Laboratory Press Biogenesis of Nuclear Bodies Miroslav Dundr1 and Tom Misteli2 1Department of Cell Biology, Rosalind Franklin University of Medicine and Science, North Chicago, Ilinois 60064 2National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892 Correspondence: [email protected]; [email protected] The nucleus is unique amongst cellular organelles in that it contains a myriad of discrete suborganelles. These nuclear bodies are morphologically and molecularly distinct entities, and they host specific nuclear processes. Although the mode of biogenesis appears to differ widely between individual nuclear bodies, several common design principles are emerging, particularly, the ability of nuclear bodies to form de novo, a role of RNA as a struc- tural element and self-organization as a mode of formation. The controlled biogenesis of nuclear bodies is essential for faithful maintenance of nuclear architecture during the cell cycle and is an important part of cellular responses to intra- and extracellular events. he mammalian cell nucleus contains a mul- seems to act indirectly by regulating the local Ttitude of discrete suborganelles, referred to concentration of its components in the nucleo- as nuclear bodies or nuclear compartments plasm. (reviewed in Dundr and Misteli 2001; Spector In many ways, nuclear bodies are similar 2001; Lamond and Spector 2003; Handwerger to conventional cellular organelles in the cy- and Gall 2006; Zhao et al. 2009). These bodies toplasm. Like cytoplasmic organelles, they con- are an essential part of the nuclear landscape tain a specific set of resident proteins, which as they compartmentalize the nuclear space defines each structure molecularly. -
Module IV Nucleus
Module IV Nucleus Structure and functions of interphase nucleus, Nuclear membrane, pore complex, structure and functions of nucleolus Chromosomes – Structure; Heterochromatin, Euchromatin, Nucleosomes, Nucleus is the most important part of the cell situated in the cytoplasm. All the cellular activities are controlled by it. Nucleus is a directing and organizing unit without which the cell could not exist. It was discovered by Robert Brown (1831) in flowering plants and is now recognized as the structure that contains the hereditary material of the cell. The study of nucleus or karyosome constitutes karyology. The location of nucleus varies in the cell depending upon the species. Usually it is situated in the centre of the cell surrounded on all sides by cytoplasm. In green algae, Acetabularia, it shows various positions, though mainly present in the basal part of cell. Generally the nuclei are scattered in the cytoplasm. Morphology: 1. Shape: The shape of nucleus is variable according to cell type. It is generally spheroid but ellipsoid or flattened nuclei may also occur in certain cells. The nuclear margins are generally smooth but they may be lobulated bearing small infoldings of nuclear membrane as in leucocytes. In certain white blood corpuscles the nucleus is dumbbell-shaped and exhibits variation during life history stages. In human neutrophil, it is trilobed. 2. Number: Mostly cell contains a single nucleus, known as mononucleate cell. Cells containing two nuclei are known as binucleate cells (e.g., Paramecium), and cells of cartilage and liver. Sometimes more than two nuclei (3 to 100 nuclei) are present in a single cell. -
Molecular Genetics of Microcephaly Primary Hereditary: an Overview
brain sciences Review Molecular Genetics of Microcephaly Primary Hereditary: An Overview Nikistratos Siskos † , Electra Stylianopoulou †, Georgios Skavdis and Maria E. Grigoriou * Department of Molecular Biology & Genetics, Democritus University of Thrace, 68100 Alexandroupolis, Greece; [email protected] (N.S.); [email protected] (E.S.); [email protected] (G.S.) * Correspondence: [email protected] † Equal contribution. Abstract: MicroCephaly Primary Hereditary (MCPH) is a rare congenital neurodevelopmental disorder characterized by a significant reduction of the occipitofrontal head circumference and mild to moderate mental disability. Patients have small brains, though with overall normal architecture; therefore, studying MCPH can reveal not only the pathological mechanisms leading to this condition, but also the mechanisms operating during normal development. MCPH is genetically heterogeneous, with 27 genes listed so far in the Online Mendelian Inheritance in Man (OMIM) database. In this review, we discuss the role of MCPH proteins and delineate the molecular mechanisms and common pathways in which they participate. Keywords: microcephaly; MCPH; MCPH1–MCPH27; molecular genetics; cell cycle 1. Introduction Citation: Siskos, N.; Stylianopoulou, Microcephaly, from the Greek word µικρoκεϕαλi´α (mikrokephalia), meaning small E.; Skavdis, G.; Grigoriou, M.E. head, is a term used to describe a cranium with reduction of the occipitofrontal head circum- Molecular Genetics of Microcephaly ference equal, or more that teo standard deviations -
Aneuploidy: Using Genetic Instability to Preserve a Haploid Genome?
Health Science Campus FINAL APPROVAL OF DISSERTATION Doctor of Philosophy in Biomedical Science (Cancer Biology) Aneuploidy: Using genetic instability to preserve a haploid genome? Submitted by: Ramona Ramdath In partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biomedical Science Examination Committee Signature/Date Major Advisor: David Allison, M.D., Ph.D. Academic James Trempe, Ph.D. Advisory Committee: David Giovanucci, Ph.D. Randall Ruch, Ph.D. Ronald Mellgren, Ph.D. Senior Associate Dean College of Graduate Studies Michael S. Bisesi, Ph.D. Date of Defense: April 10, 2009 Aneuploidy: Using genetic instability to preserve a haploid genome? Ramona Ramdath University of Toledo, Health Science Campus 2009 Dedication I dedicate this dissertation to my grandfather who died of lung cancer two years ago, but who always instilled in us the value and importance of education. And to my mom and sister, both of whom have been pillars of support and stimulating conversations. To my sister, Rehanna, especially- I hope this inspires you to achieve all that you want to in life, academically and otherwise. ii Acknowledgements As we go through these academic journeys, there are so many along the way that make an impact not only on our work, but on our lives as well, and I would like to say a heartfelt thank you to all of those people: My Committee members- Dr. James Trempe, Dr. David Giovanucchi, Dr. Ronald Mellgren and Dr. Randall Ruch for their guidance, suggestions, support and confidence in me. My major advisor- Dr. David Allison, for his constructive criticism and positive reinforcement. -
Nuclear Pore Complexes and Nucleocytoplasmic Exchange
Pore Relations: Nuclear Pore Complexes and Nucleocytoplasmic Exchange Michael P. Rout and John D. Aitchison Laboratory of Cellular and Structural Biology The Rockefeller University, 1230 York Ave, New York, NY 10021 USA [email protected] 212 327 8135 Department of Cell Biology University of Alberta Edmonton, Alberta T6G 2H7 Canada [email protected] 780 492 6062 1 Introduction One of the main characteristics distinguishing eukaryotes from prokaryotes is that eukaryotes compartmentalize many life processes within membrane bound organelles. The most obvious of these is the nucleus, bounded by a double-membraned nuclear envelope (NE). The NE thus acts as a barrier separating the nucleoplasm from the cytoplasm. An efficient, regulated and continuous exchange system between the nucleoplasm and cytoplasm is therefore necessary to maintain the structures of the nucleus and the communication between the genetic material and the rest of the cell. The sole mediators of this exchange are the nuclear pore complexes (NPCs), large proteinaceous assemblies embedded within reflexed pores of the NE membranes (Davis, 1995). While small molecules (such as nucleotides, water and ions) can freely diffuse across the NPCs, macromolecules such as proteins and ribonucleoprotein (RNP) particles are actively transported in a highly regulated and selective manner. Transport through the NPC requires specific soluble factors which recognize transport substrates in either the nucleoplasm or cytoplasm and mediate their transport by docking them to specific components of the NPC (Mattaj and Englmeier, 1998). In order to understand how transport works, we must first catalog the soluble transport factors and NPC components, and then study the details of how they interact. -
NLS-Mediated NPC Functions of the Nucleoporin Pom121
FEBS Letters 584 (2010) 3292–3298 journal homepage: www.FEBSLetters.org NLS-mediated NPC functions of the nucleoporin Pom121 Sevil Yavuz, Rachel Santarella-Mellwig, Birgit Koch, Andreas Jaedicke, Iain W. Mattaj *,1, Wolfram Antonin **,1 European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany article info abstract Article history: RanGTP mediates nuclear import and mitotic spindle assembly by dissociating import receptors Received 23 February 2010 from nuclear localization signal (NLS) bearing proteins. We investigated the interplay between Revised 31 May 2010 import receptors and the transmembrane nucleoporin Pom121. We found that Pom121 interacts Accepted 2 July 2010 with importin a/b and a group of nucleoporins in an NLS-dependent manner. In vivo, replacement Available online 14 July 2010 of Pom121 with an NLS mutant version resulted in defective nuclear transport, induction of aber- Edited by Ulrike Kuttay rant cytoplasmic membrane stacks and decreased cell viability. We propose that the NLS sites of Pom121 affect its function in NPC assembly both by influencing nucleoporin interactions and pore membrane structure. Keywords: Pom121 Nucleoporin Structured summary: Importin MINT-7951230: pom121 (uniprotkb:Q5EWX9) physically interacts (MI:0914) with nup155 (uni- protkb:O75694), Nup133 (uniprotkb:Q8WUM0) and Importin beta (uniprotkb:Q14974) by pull down (MI:0096) MINT-7951210: pom121 (uniprotkb:Q5EWX9) physically interacts (MI:0915) with Importin alpha (uni- protkb:P52170) and Importin beta (uniprotkb:P52297) -
Cytochemical Features Common to Nucleoli and Cytoplasmic Nucleoloids of Olea Europaea Meiocytes: Detection of Rrna by in Situ Hybridization
Journal of Cell Science 107, 621-629 (1994) 621 Printed in Great Britain © The Company of Biologists Limited 1994 JCS8341 Cytochemical features common to nucleoli and cytoplasmic nucleoloids of Olea europaea meiocytes: detection of rRNA by in situ hybridization J. D. Alché, M. C. Fernández and M. I. Rodríguez-García* Plant Biochemistry, Molecular and Cellular Biology Department, Estación Experimental del Zaidín, CSIC, Profesor Albareda 1, E- 18008 Granada, Spain *Author for correspondence SUMMARY We used light and electron microscopic techniques to study highly phosphorylated proteins. Immunohistochemical the composition of cytoplasmic nucleoloids during meiotic techniques failed to detect DNA in either structure. In situ division in Olea europaea. Nucleoloids were found in two hybridization to a 18 S rRNA probe demonstrated the clearly distinguishable morphological varieties: one similar presence of ribosomal transcripts in both the nucleolus and in morphology to the nucleolus, and composed mainly of nucleoloids. These similarities in morphology and compo- dense fibrillar component, and another surrounded by sition may reflect similar functionalities. many ribosome-like particles. Cytochemical and immuno- cytochemical techniques showed similar reactivities in nucleoloids and the nucleolus: both are ribonucleoproteic Key words: nucleoloids, nucleolar proteins, rRNA, in situ in nature, and possess argyrophillic, argentaffinic and hybridization INTRODUCTION lentum (Carretero and Rodríguez-García, unpublished observa- tions). The reason for this diversity is unknown. Cytoplasmic bodies similar in morphology and ultrastructural Nucleoloids have rarely been studied in genera other than characteristics to the nucleolus have been reported many times Lilium. Cytoplasmic nucleoloids are very common in Olea in relation to plant meiosis (Latter, 1926; Frankel, 1937; europaea during microsporogenesis and their large size and Hakansson and Levan, 1942; Gavaudan, 1948; Lindemann, peculiar morphological characteristics make them a good 1956). -
The Sub-Nuclear Localization of RNA-Binding Proteins in KSHV-Infected Cells
cells Article The Sub-Nuclear Localization of RNA-Binding Proteins in KSHV-Infected Cells Ella Alkalay, Chen Gam Ze Letova Refael, Irit Shoval, Noa Kinor, Ronit Sarid and Yaron Shav-Tal * The Mina & Everard Goodman Faculty of Life Sciences and The Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat Gan 5290002, Israel; [email protected] (E.A.); [email protected] (C.G.Z.L.R.); [email protected] (I.S.); [email protected] (N.K.); [email protected] (R.S.) * Correspondence: [email protected] Received: 14 August 2020; Accepted: 21 August 2020; Published: 25 August 2020 Abstract: RNA-binding proteins, particularly splicing factors, localize to sub-nuclear domains termed nuclear speckles. During certain viral infections, as the nucleus fills up with replicating virus compartments, host cell chromatin distribution changes, ending up condensed at the nuclear periphery. In this study we wished to determine the fate of nucleoplasmic RNA-binding proteins and nuclear speckles during the lytic cycle of the Kaposi’s sarcoma associated herpesvirus (KSHV). We found that nuclear speckles became fewer and dramatically larger, localizing at the nuclear periphery, adjacent to the marginalized chromatin. Enlarged nuclear speckles contained splicing factors, whereas other proteins were nucleoplasmically dispersed. Polyadenylated RNA, typically found in nuclear speckles under regular conditions, was also found in foci separated from nuclear speckles in infected cells. Poly(A) foci did not contain lncRNAs known to colocalize with nuclear speckles but contained the poly(A)-binding protein PABPN1. Examination of the localization of spliced viral RNAs revealed that some spliced transcripts could be detected within the nuclear speckles. -
Lecture9'21 Chromatin II
Genetic Organization -Chromosomal Arrangement: From Form to Function. Chapters 9 & 10 in Genes XI The Eukaryotic chromosome – Organized Structures -banding – Centromeres – Telomeres – Nucleosomes – Euchromatin / Heterochromatin – Higher Orders of Chromosomal Structure 2 Heterochromatin differs from euchromatin in that heterochromatin is effectively inert; remains condensed during interphase; is transcriptionally repressed; replicates late in S phase and may be localized to the centromere or nuclear periphery Facultative heterochromatin is not restricted by pre-designated sequence; genes that are moved within or near heterochromatic regions can become inactivated as a result of their new location. Heterochromatin differs from euchromatin in that heterochromatin is effectively inert; remains condensed during interphase; is transcriptionally repressed; replicates late in S phase and may be localized to the centromere or nuclear periphery Facultative heterochromatin is not restricted by pre-designated sequence; genes that are moved within or near heterochromatic regions can become inactivated as a result of their new location. Chromatin inactivation (or heterochromatin formation) occurs by the addition of proteins to the nucleosomal fiber. May be due to: Chromatin condensation -making it inaccessible to transcriptional apparatus Proteins that accumulate and inhibit accessibility to the regulatory sequences Proteins that directly inhibit transcription Chromatin Is Fundamentally Divided into Euchromatin and Heterochromatin • Individual chromosomes can be seen only during mitosis. • During interphase, the general mass of chromatin is in the form of euchromatin, which is slightly less tightly packed than mitotic chromosomes. TF20210119 Regions of compact heterochromatin are clustered near the nucleolus and nuclear membrane Photo courtesy of Edmund Puvion, Centre National de la Recherche Scientifique Chromatin: Basic Structures • nucleosome – The basic structural subunit of chromatin, consisting of ~200 bp of DNA wrapped around an octamer of histone proteins. -
Nuclear Pore Complexes Cluster in Dysmorphic Nuclei of Normal and Progeria Cells During Replicative Senescence
Nuclear Pore Complexes Cluster in Dysmorphic Nuclei of Normal and Progeria Cells during Replicative Senescence Jennifer M. Röhrl, Rouven Arnold and Karima Djabali * Epigenetics of Aging, Department of Dermatology and Allergy, TUM School of Medicine, Technical University of Munich (TUM), 85748 Garching, Germany; [email protected] (J.M.R.); [email protected] (R.A.) * Correspondence: [email protected] Supplementary Figures Figure S1: Seeding of NPCs, by ELYS on anaphase chromosomes was not affected in HGPS. Immunocytochemistry of (a) control (GMO1652c) and (b) HGPS (HGADFN003) fibroblasts using α‐ELYS and α‐LA antibody, counterstained with DAPI. NPCs cluster in interphase HGPS cells (b), unlike the evenly distributed punctate pattern in interphase control cells (a). Recruitment of ELYS to anaphase chromosomes is not affected in HGPS cells, compared to control. No defect in ELYS localization can be observed in HGPS from prophase to cytokinesis. NPC, nuclear pore complex; HGPS, Hutchinson‐Gilford progeria. n ≥3. Figure S2: Recruitment of basket nucleoporin NUP153 and scaffold nucleoporin NUP107 were not affected in HGPS. Immunocytochemistry of (a) control (GMO1652c) and (b) HGPS (HGADFN003) fibroblasts using α‐ NUP107 and α‐NUP153 antibodies, counterstained with DAPI. NPCs cluster in interphase HGPS cells (b), unlike the evenly spread out punctate pattern in control interphase (a). Recruitment of NUP153 to anaphase chromosomes is not affected in HGPS cells, compared to the control. No defect in NUP153 or NUP107 localization can be observed in HGPS from prophase to cytokinesis. n ≥3. Figure S3: SUN1 aggregates did not colocalize with mAb414. Immunocytochemistry of (a) control (GMO1652c) and (b) HGPS (HGADFN003) fibroblasts using mAb414 and α‐SUN1 antibodies, counterstained with DAPI.