The Nuclear Envelope
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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 -
A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated. -
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. -
Actin Nucleator Spire 1 Is a Regulator of Ectoplasmic Specialization in the Testis Qing Wen1,Nanli1,Xiangxiao 1,2,Wing-Yeelui3, Darren S
Wen et al. Cell Death and Disease (2018) 9:208 DOI 10.1038/s41419-017-0201-6 Cell Death & Disease ARTICLE Open Access Actin nucleator Spire 1 is a regulator of ectoplasmic specialization in the testis Qing Wen1,NanLi1,XiangXiao 1,2,Wing-yeeLui3, Darren S. Chu1, Chris K. C. Wong4, Qingquan Lian5,RenshanGe5, Will M. Lee3, Bruno Silvestrini6 and C. Yan Cheng 1 Abstract Germ cell differentiation during the epithelial cycle of spermatogenesis is accompanied by extensive remodeling at the Sertoli cell–cell and Sertoli cell–spermatid interface to accommodate the transport of preleptotene spermatocytes and developing spermatids across the blood–testis barrier (BTB) and the adluminal compartment of the seminiferous epithelium, respectively. The unique cell junction in the testis is the actin-rich ectoplasmic specialization (ES) designated basal ES at the Sertoli cell–cell interface, and the apical ES at the Sertoli–spermatid interface. Since ES dynamics (i.e., disassembly, reassembly and stabilization) are supported by actin microfilaments, which rapidly converts between their bundled and unbundled/branched configuration to confer plasticity to the ES, it is logical to speculate that actin nucleation proteins play a crucial role to ES dynamics. Herein, we reported findings that Spire 1, an actin nucleator known to polymerize actins into long stretches of linear microfilaments in cells, is an important regulator of ES dynamics. Its knockdown by RNAi in Sertoli cells cultured in vitro was found to impede the Sertoli cell tight junction (TJ)-permeability barrier through changes in the organization of F-actin across Sertoli cell cytosol. Unexpectedly, Spire 1 knockdown also perturbed microtubule (MT) organization in Sertoli cells cultured in vitro. -
Applying Expression Profile Similarity for Discovery of Patient-Specific
bioRxiv preprint doi: https://doi.org/10.1101/172015; this version posted September 17, 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 4.0 International license. Applying expression profile similarity for discovery of patient-specific functional mutations Guofeng Meng Partner Institute of Computational Biology, Yueyang 333, Shanghai, China email: [email protected] Abstract The progress of cancer genome sequencing projects yields unprecedented information of mutations for numerous patients. However, the complexity of mutation profiles of patients hinders the further understanding of mechanisms of oncogenesis. One basic question is how to uncover mutations with functional impacts. In this work, we introduce a computational method to predict functional somatic mutations for each of patient by integrating mutation recurrence with similarity of expression profiles of patients. With this method, the functional mutations are determined by checking the mutation enrichment among a group of patients with similar expression profiles. We applied this method to three cancer types and identified the functional mutations. Comparison of the predictions for three cancer types suggested that most of the functional mutations were cancer-type-specific with one exception to p53. By checking prediction results, we found that our method effectively filtered non-functional mutations resulting from large protein sizes. In addition, this methods can also perform functional annotation to each patient to describe their association with signalling pathways or biological processes. In breast cancer, we predicted "cell adhesion" and other mutated gene associated terms to be significantly enriched among patients. -
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 -
Cldn19 Clic2 Clmp Cln3
NewbornDx™ Advanced Sequencing Evaluation When time to diagnosis matters, the NewbornDx™ Advanced Sequencing Evaluation from Athena Diagnostics delivers rapid, 5- to 7-day results on a targeted 1,722-genes. A2ML1 ALAD ATM CAV1 CLDN19 CTNS DOCK7 ETFB FOXC2 GLUL HOXC13 JAK3 AAAS ALAS2 ATP1A2 CBL CLIC2 CTRC DOCK8 ETFDH FOXE1 GLYCTK HOXD13 JUP AARS2 ALDH18A1 ATP1A3 CBS CLMP CTSA DOK7 ETHE1 FOXE3 GM2A HPD KANK1 AASS ALDH1A2 ATP2B3 CC2D2A CLN3 CTSD DOLK EVC FOXF1 GMPPA HPGD K ANSL1 ABAT ALDH3A2 ATP5A1 CCDC103 CLN5 CTSK DPAGT1 EVC2 FOXG1 GMPPB HPRT1 KAT6B ABCA12 ALDH4A1 ATP5E CCDC114 CLN6 CUBN DPM1 EXOC4 FOXH1 GNA11 HPSE2 KCNA2 ABCA3 ALDH5A1 ATP6AP2 CCDC151 CLN8 CUL4B DPM2 EXOSC3 FOXI1 GNAI3 HRAS KCNB1 ABCA4 ALDH7A1 ATP6V0A2 CCDC22 CLP1 CUL7 DPM3 EXPH5 FOXL2 GNAO1 HSD17B10 KCND2 ABCB11 ALDOA ATP6V1B1 CCDC39 CLPB CXCR4 DPP6 EYA1 FOXP1 GNAS HSD17B4 KCNE1 ABCB4 ALDOB ATP7A CCDC40 CLPP CYB5R3 DPYD EZH2 FOXP2 GNE HSD3B2 KCNE2 ABCB6 ALG1 ATP8A2 CCDC65 CNNM2 CYC1 DPYS F10 FOXP3 GNMT HSD3B7 KCNH2 ABCB7 ALG11 ATP8B1 CCDC78 CNTN1 CYP11B1 DRC1 F11 FOXRED1 GNPAT HSPD1 KCNH5 ABCC2 ALG12 ATPAF2 CCDC8 CNTNAP1 CYP11B2 DSC2 F13A1 FRAS1 GNPTAB HSPG2 KCNJ10 ABCC8 ALG13 ATR CCDC88C CNTNAP2 CYP17A1 DSG1 F13B FREM1 GNPTG HUWE1 KCNJ11 ABCC9 ALG14 ATRX CCND2 COA5 CYP1B1 DSP F2 FREM2 GNS HYDIN KCNJ13 ABCD3 ALG2 AUH CCNO COG1 CYP24A1 DST F5 FRMD7 GORAB HYLS1 KCNJ2 ABCD4 ALG3 B3GALNT2 CCS COG4 CYP26C1 DSTYK F7 FTCD GP1BA IBA57 KCNJ5 ABHD5 ALG6 B3GAT3 CCT5 COG5 CYP27A1 DTNA F8 FTO GP1BB ICK KCNJ8 ACAD8 ALG8 B3GLCT CD151 COG6 CYP27B1 DUOX2 F9 FUCA1 GP6 ICOS KCNK3 ACAD9 ALG9 -
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. -
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.