Structure-Function Relationships of Nuclear Lamins Shalaka Patil and Kundan Sengupta *
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For the Safe Delivery of Essential Proteins
Dedicated ‘Bodyguards’ for the Safe Delivery of Essential Proteins Dr Brigitte Pertschy DEDICATED ‘BODYGUARDS’ FOR THE SAFE DELIVERY OF ESSENTIAL PROTEINS Ribosomes are undoubtedly one of the most essential cellular components in life. These macromolecules are responsible for the synthesis of proteins in all living cells. Dr Brigitte Pertschy, Dr Ingrid Rössler and Jutta Hafner at the Institute of Molecular Biosciences at the University of Graz, Austria, have discovered that the safe delivery of essential ribosomal proteins that make up the ribosomes is dependant on ‘private bodyguards’ or ‘chaperones’. Nascent Ribosomal Proteins Journey Ribosome synthesis is an important of their synthesis and proper folding Across the Cell to the Nucleus and continuous process. Dr Pertschy of the proteins. Importins have also describes that a growing cell requires been reported as aides in the import of The ribosome is the intricate nano- up to 1,000 ribosomes to be synthesised proteins to the cell nucleus as well as in machinery that translates messenger per minute. The r-proteins are protecting proteins from aggregation. RNA strands (mRNA) into protein. Our produced in the cell cytoplasm by the DNA holds the instructions for building ribosome itself (that way, the ribosome The team speculated that since every protein needed for our bodies to participates in its own reproduction). r-proteins are produced at extremely function. Initially, DNA is transcribed From there the r-proteins must travel high amounts and their correct into mRNA, which contains the amino to the cell nucleus where in a complex functioning is so critical for a cell, these acid sequence of a particular protein. -
Revealing the Mechanism of Xist-Mediated Silencing
Revealing the Mechanism of Xist-mediated Silencing Thesis by Chun-Kan Chen In Partial Fulfillment of the Requirements for the degree of Doctor of Philosophy CALIFORNIA INSTITUTE OF TECHNOLOGY Pasadena, California 2018 Defended November 1, 2017 ii 2017 Chun-Kan Chen ORCID: 0000-0002-1194-9137 iii ACKNOWLEDGEMENTS First of all, I’d like to thank my great mentor, Dr. Mitch Guttman (California Institute of Technology, Pasadena, CA), who led me to become an independent researcher and gave me valuable advice that guided me to accomplish this thesis. He has always been supportive of my future plans and career goals. I really enjoyed every discussion we have had. We often generated some interesting ideas for projects during our discussions. I would also like to send my thanks to my lab mates, Amy Chow, Mario Blanco, and Erik Aznauryan, who helped me with many experiments to move the project forward. I’d like to acknowledge Dr. Kathrin Plath (University of California, Los Angeles, Los Angeles, CA) for the collaboration and his critical comments on this project. Also, I want to thank Jesse Engreitz and Patrick McDonel, who provided helpful comments and suggestions to the project. I want to thank my parents, brother, and parents-in-law who provided both instrumental and emotional support to assist me in completing my Ph.D. degree. I also want to thank my friends, Lily Chen, Pei-Ying Lin, Tzu-Yao Wang, and Wei Li, for giving me valuable social support during my years in graduate school. Last but not least, I would like to send my special thanks to my wife, Christine Juang, who has always been supportive. -
Differential Expression of Two Neuronal Intermediate-Filament Proteins, Peripherin and the Low-Molecular-Mass Neurofilament Prot
The Journal of Neuroscience, March 1990, fO(3): 764-764 Differential Expression of Two Neuronal Intermediate-Filament Proteins, Peripherin and the Low-Molecular-Mass Neurofilament Protein (NF-L), During the Development of the Rat Michel Escurat,’ Karima Djabali,’ Madeleine Gumpel,2 Franqois Gras,’ and Marie-Madeleine Portier’ lCollBne de France, Biochimie Cellulaire, 75231 Paris Cedex 05, France, *HBpital de la Salpktricke, Unite INSERM 134, 75651Paris Cedex 13, France The expression of peripherin, an intermediate filament pro- and Freeman, 1978), now more generally referred to respectively tein, had been shown by biochemical methods to be local- as high-, middle-, and low-molecular-mass NFP (NF-H, NF-M, ized in the neurons of the PNS. Using immunohistochemical and NF-L). These proteins are expressed in most mature neu- methods, we analyzed this expression more extensively dur- ronal populations belonging either to the CNS or to the PNS; ing the development of the rat and compared it with that of developing neurons generally do not express any of them until the low-molecular-mass neurofilament protein (NF-L), which they become postmitotic (Tapscott et al., 198 la). is expressed in every neuron of the CNS and PNS. We, however, described another IFP with a molecular weight The immunoreactivity of NF-L is first apparent at the 25 of about 57 kDa, which we had first observed in mouse neu- somite stage (about 11 d) in the ventral horn of the spinal roblastoma cell lines and which was also expressed in rat pheo- medulla and in the posterior part of the rhombencephalon. chromocytoma PC1 2 cell line. -
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. -
Upon Microbial Challenge, Human Neutrophils Undergo Rapid Changes in Nuclear Architecture and Chromatin Folding to Orchestrate an Immediate Inflammatory Gene Program
Downloaded from genesdev.cshlp.org on October 5, 2021 - Published by Cold Spring Harbor Laboratory Press Upon microbial challenge, human neutrophils undergo rapid changes in nuclear architecture and chromatin folding to orchestrate an immediate inflammatory gene program Matthew Denholtz,1,5 Yina Zhu,1,5 Zhaoren He,1 Hanbin Lu,1 Takeshi Isoda,1,4 Simon Döhrmann,2 Victor Nizet,2,3 and Cornelis Murre1 1Division of Biological Sciences, Department of Molecular Biology, University of California at San Diego, La Jolla, California 92039, USA; 2Department of Pediatrics, University of California at San Diego School of Medicine, La Jolla, California 92093, USA; 3Skaggs School of Pharmaceutical Sciences, University of California at San Diego, La Jolla, California 92093, USA Differentiating neutrophils undergo large-scale changes in nuclear morphology. How such alterations in structure are established and modulated upon exposure to microbial agents is largely unknown. Here, we found that prior to encounter with bacteria, an armamentarium of inflammatory genes was positioned in a transcriptionally passive environment suppressing premature transcriptional activation. Upon microbial exposure, however, human neu- trophils rapidly (<3 h) repositioned the ensemble of proinflammatory genes toward the transcriptionally permissive compartment. We show that the repositioning of genes was closely associated with the swift recruitment of cohesin across the inflammatory enhancer landscape, permitting an immediate transcriptional response upon bacterial exposure. We found that activated enhancers, marked by increased deposition of H3K27Ac, were highly enriched for cistromic elements associated with PU.1, CEBPB, TFE3, JUN, and FOSL2 occupancy. These data reveal how upon microbial challenge the cohesin machinery is recruited to an activated enhancer repertoire to instruct changes in chromatin folding, nuclear architecture, and to activate an inflammatory gene program. -
Introduction to the Cell Cell History Cell Structures and Functions
Introduction to the cell cell history cell structures and functions CK-12 Foundation December 16, 2009 CK-12 Foundation is a non-profit organization with a mission to reduce the cost of textbook materials for the K-12 market both in the U.S. and worldwide. Using an open-content, web-based collaborative model termed the “FlexBook,” CK-12 intends to pioneer the generation and distribution of high quality educational content that will serve both as core text as well as provide an adaptive environment for learning. Copyright ©2009 CK-12 Foundation This work is licensed under the Creative Commons Attribution-Share Alike 3.0 United States License. To view a copy of this license, visit http://creativecommons.org/licenses/by-sa/3.0/us/ or send a letter to Creative Commons, 171 Second Street, Suite 300, San Francisco, California, 94105, USA. Contents 1 Cell structure and function dec 16 5 1.1 Lesson 3.1: Introduction to Cells .................................. 5 3 www.ck12.org www.ck12.org 4 Chapter 1 Cell structure and function dec 16 1.1 Lesson 3.1: Introduction to Cells Lesson Objectives • Identify the scientists that first observed cells. • Outline the importance of microscopes in the discovery of cells. • Summarize what the cell theory proposes. • Identify the limitations on cell size. • Identify the four parts common to all cells. • Compare prokaryotic and eukaryotic cells. Introduction Knowing the make up of cells and how cells work is necessary to all of the biological sciences. Learning about the similarities and differences between cell types is particularly important to the fields of cell biology and molecular biology. -
Nuclear Domains
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Cold Spring Harbor Laboratory Institutional Repository CELL SCIENCE AT A GLANCE 2891 Nuclear domains dynamic structures and, in addition, nuclear pore complex has been shown to rapid protein exchange occurs between have a remarkable substructure, in which David L. Spector many of the domains and the a basket extends into the nucleoplasm. Cold Spring Harbor Laboratory, One Bungtown nucleoplasm (Misteli, 2001). An The peripheral nuclear lamina lies Road, Cold Spring Harbor, NY 11724, USA extensive effort is currently underway by inside the nuclear envelope and is (e-mail: [email protected]) numerous laboratories to determine the composed of lamins A/C and B and is biological function(s) associated with thought to play a role in regulating Journal of Cell Science 114, 2891-2893 (2001) © The Company of Biologists Ltd each domain. The accompanying poster nuclear envelope structure and presents an overview of commonly anchoring interphase chromatin at the The mammalian cell nucleus is a observed nuclear domains. nuclear periphery. Internal patches of membrane-bound organelle that contains lamin protein are also present in the the machinery essential for gene The nucleus is bounded by a nuclear nucleoplasm (Moir et al., 2000). The expression. Although early studies envelope, a double-membrane structure, cartoon depicts much of the nuclear suggested that little organization exists of which the outer membrane is envelope/peripheral lamina as within this compartment, more contiguous with the rough endoplasmic transparent, so that internal structures contemporary studies have identified an reticulum and is often studded with can be more easily observed. -
Tubulin: Are They Linced?
cells Review Microtubular and Nuclear Functions of γ-Tubulin: Are They LINCed? Jana Chumová, Hana Kourová, Lucie Trögelová, Petr Halada and Pavla Binarová * Institute of Microbiology of the Czech Academy of Sciences, Vídeˇnská 1083, 142 20 Prague, Czech Republic; [email protected] (J.C.); [email protected] (H.K.); [email protected] (L.T.); [email protected] (P.H.) * Correspondence: [email protected]; Tel.: +420-241-062-130 Received: 8 February 2019; Accepted: 14 March 2019; Published: 19 March 2019 Abstract: γ-Tubulin is a conserved member of the tubulin superfamily with a function in microtubule nucleation. Proteins of γ-tubulin complexes serve as nucleation templates as well as a majority of other proteins contributing to centrosomal and non-centrosomal nucleation, conserved across eukaryotes. There is a growing amount of evidence of γ-tubulin functions besides microtubule nucleation in transcription, DNA damage response, chromatin remodeling, and on its interactions with tumor suppressors. However, the molecular mechanisms are not well understood. Furthermore, interactions with lamin and SUN proteins of the LINC complex suggest the role of γ-tubulin in the coupling of nuclear organization with cytoskeletons. γ-Tubulin that belongs to the clade of eukaryotic tubulins shows characteristics of both prokaryotic and eukaryotic tubulins. Both human and plant γ-tubulins preserve the ability of prokaryotic tubulins to assemble filaments and higher-order fibrillar networks. γ-Tubulin filaments, with bundling and aggregating capacity, are suggested to perform complex scaffolding and sequestration functions. In this review, we discuss a plethora of γ-tubulin molecular interactions and cellular functions, as well as recent advances in understanding the molecular mechanisms behind them. -
SMC Complexes Orchestrate the Mitotic Chromatin Interaction Landscape
Curr Genet DOI 10.1007/s00294-017-0755-y REVIEW SMC complexes orchestrate the mitotic chromatin interaction landscape Yasutaka Kakui1 · Frank Uhlmann1 Received: 13 September 2017 / Revised: 14 September 2017 / Accepted: 16 September 2017 © The Author(s) 2017. This article is an open access publication Abstract Chromatin is a very long DNA–protein complex Keywords Chromosome condensation · SMC complex · that controls the expression and inheritance of the genetic Chromatin · Cell cycle · Hi-C information. Chromatin is stored within the nucleus in interphase and further compacted into chromosomes dur- ing mitosis. This process, known as chromosome condensa- Introduction tion, is essential for faithful segregation of genomic DNA into daughter cells. Condensin and cohesin, members of How chromatin is spatially organized within the cell nucleus the structural maintenance of chromosomes (SMC) fam- and within chromosomes is a fundamental question in cell ily, are fundamental for chromosome architecture, both biology. Centimeter-long DNA molecules change their spa- for establishment of chromatin structure in the interphase tial chromatin organization within micrometer-sized cells nucleus and for the formation of condensed chromosomes during cell cycle progression. In interphase, chromatin is in mitosis. These ring-shaped SMC complexes are thought distributed throughout the nucleus to express the genetic to regulate the interactions between DNA strands by topo- information. When cells enter mitosis, chromatin becomes logically entrapping DNA. How this activity shapes chro- compacted to form mitotic chromosomes. Chromosome mosomes is not yet understood. Recent high throughput condensation, the gross morphological change of spatial chromosome conformation capture studies revealed how chromatin organization in mitosis, is indispensable for chromatin is reorganized during the cell cycle and have the faithful inheritance of genetic information. -
Lamin A/C Cardiomyopathy: Implications for Treatment
Current Cardiology Reports (2019) 21:160 https://doi.org/10.1007/s11886-019-1224-7 MYOCARDIAL DISEASE (A ABBATE AND G SINAGRA, SECTION EDITORS) Lamin A/C Cardiomyopathy: Implications for Treatment Suet Nee Chen1 & Orfeo Sbaizero1,2 & Matthew R. G. Taylor1 & Luisa Mestroni1 # Springer Science+Business Media, LLC, part of Springer Nature 2019 Abstract Purpose of Review The purpose of this review is to provide an update on lamin A/C (LMNA)-related cardiomyopathy and discuss the current recommendations and progress in the management of this disease. LMNA-related cardiomyopathy, an inherited autosomal dominant disease, is one of the most common causes of dilated cardiomyopathy and is characterized by steady progression toward heart failure and high risks of arrhythmias and sudden cardiac death. Recent Findings We discuss recent advances in the understanding of the molecular mechanisms of the disease including altered cell biomechanics, which may represent novel therapeutic targets to advance the current management approach, which relies on standard heart failure recommendations. Future therapeutic approaches include repurposed molecularly directed drugs, siRNA- based gene silencing, and genome editing. Summary LMNA-related cardiomyopathy is the focus of active in vitro and in vivo research, which is expected to generate novel biomarkers and identify new therapeutic targets. LMNA-related cardiomyopathy trials are currently underway. Keywords Lamin A/C gene . Laminopathy . Heart failure . Arrhythmias . Mechanotransduction . P53 . CRISPR–Cas9 therapy Introduction functions, including maintaining nuclear structural integrity, regulating gene expression, mechanosensing, and Mutations in the lamin A/C gene (LMNA)causelaminopathies, mechanotransduction through the lamina-associated proteins a heterogeneous group of inherited disorders including muscu- [6–11]. -
DEAD-Box RNA Helicases in Cell Cycle Control and Clinical Therapy
cells Review DEAD-Box RNA Helicases in Cell Cycle Control and Clinical Therapy Lu Zhang 1,2 and Xiaogang Li 2,3,* 1 Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan 430060, China; [email protected] 2 Department of Internal Medicine, Mayo Clinic, 200 1st Street, SW, Rochester, MN 55905, USA 3 Department of Biochemistry and Molecular Biology, Mayo Clinic, 200 1st Street, SW, Rochester, MN 55905, USA * Correspondence: [email protected]; Tel.: +1-507-266-0110 Abstract: Cell cycle is regulated through numerous signaling pathways that determine whether cells will proliferate, remain quiescent, arrest, or undergo apoptosis. Abnormal cell cycle regula- tion has been linked to many diseases. Thus, there is an urgent need to understand the diverse molecular mechanisms of how the cell cycle is controlled. RNA helicases constitute a large family of proteins with functions in all aspects of RNA metabolism, including unwinding or annealing of RNA molecules to regulate pre-mRNA, rRNA and miRNA processing, clamping protein complexes on RNA, or remodeling ribonucleoprotein complexes, to regulate gene expression. RNA helicases also regulate the activity of specific proteins through direct interaction. Abnormal expression of RNA helicases has been associated with different diseases, including cancer, neurological disorders, aging, and autosomal dominant polycystic kidney disease (ADPKD) via regulation of a diverse range of cellular processes such as cell proliferation, cell cycle arrest, and apoptosis. Recent studies showed that RNA helicases participate in the regulation of the cell cycle progression at each cell cycle phase, including G1-S transition, S phase, G2-M transition, mitosis, and cytokinesis. -
Multiple Controls Regulate Nucleostemin Partitioning Between Nucleolus and Nucleoplasm
5124 Research Article Multiple controls regulate nucleostemin partitioning between nucleolus and nucleoplasm Lingjun Meng1, Hiroaki Yasumoto1 and Robert Y. L. Tsai1,* 1Center for Cancer and Stem Cell Biology, Alkek Institute of Biosciences and Technology, Texas A&M Health Science Center, 2121 W Holcombe Blvd, Houston, TX 77030-3303, USA *Author for correspondence (e-mail: [email protected]) Accepted 6 October 2006 Journal of Cell Science 119, 5124-5136 Published by The Company of Biologists 2006 doi:10.1242/jcs.03292 Summary Nucleostemin plays an essential role in maintaining the nucleostemin. It interacts with both the basic and the GTP- continuous proliferation of stem cells and cancer cells. The binding domains of nucleostemin through a non-nucleolus- movement of nucleostemin between the nucleolus and the targeting region. Overexpression of the nucleolus-targeting nucleoplasm provides a dynamic way to partition the domain of RSL1D1 alone disperses nucleolar nucleostemin. nucleostemin protein between these two compartments. Loss of RSL1D1 expression reduces the compartmental size Here, we show that nucleostemin contains two nucleolus- and amount of nucleostemin in the nucleolus. Our work targeting regions, the basic and the GTP-binding domains, reveals that the partitioning of nucleostemin employs that exhibit a short and a long nucleolar retention time, complex mechanisms involving both nucleolar and respectively. In a GTP-unbound state, the nucleolus- nucleoplasmic components, and provides insight into the targeting activity of nucleostemin is blocked by a post-translational regulation of its activity. mechanism that traps its intermediate domain in the nucleoplasm. A nucleostemin-interacting protein, RSL1D1, Supplementary material available online at was identified that contains a ribosomal L1-domain.