DOCSLIB.ORG

Lamin B1 Is Required for Mouse Development and Nuclear Integrity

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Lamin B1 Is Required for Mouse Development and Nuclear Integrity Lamin B1 is required for mouse development and nuclear integrity Laurent Vergnes*†, Miklo´ sPe´ terfy*†, Martin O. Bergo‡, Stephen G. Young‡§, and Karen Reue*†¶ʈ *Veterans Affairs Greater Los Angeles Healthcare System and Departments of †Medicine and ¶Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90073; and ‡The Gladstone Institute of Cardiovascular Disease and §Department of Medicine, University of California, San Francisco, CA 94141 Edited by Francis S. Collins, National Institutes of Health, Bethesda, MD, and approved June 1, 2004 (received for review February 27, 2004) Lamins are key structural components of the nuclear lamina, an expression patterns and different assembly properties, suggest- intermediate filament meshwork that lies beneath the inner nu- ing independent functions. For example, B-type lamins are clear membrane. Lamins play a role in nuclear architecture, DNA expressed throughout development, whereas A-type lamins are replication, and gene expression. Mutations affecting A-type expressed only after commitment of cells to a particular differ- lamins have been associated with a variety of human diseases, entiation pathway (10, 11). Also, A- and B-type lamins exhibit including muscular dystrophy, cardiomyopathy, lipodystrophy, distinct solubility properties during mitosis because of temporal and progeria, but mutations in B-type lamins have never been differences in the association with chromatin, with the associa- identified in humans or in experimental animals. To investigate the tion of B-type lamins preceding that of the A-type lamins (12). in vivo function of lamin B1, the major B-type lamin, we generated Mutations in LMNA produce an intriguingly diverse spectrum mice with an insertional mutation in Lmnb1. The mutation resulted of diseases including muscular dystrophies (Emery–Dreifuss in the synthesis of a mutant lamin B1 protein lacking several key muscular dystrophy, limb-girdle muscular dystrophy type 1B), functional domains, including a portion of the rod domain, the neuropathy (Charcot-Marie-Tooth disease type 2), dilated car- nuclear localization signal, and the CAAX motif (the carboxyl- diomyopathy with conduction system disease, familial partial terminal signal for farnesylation). Homozygous Lmnb1 mutant lipodystrophy (s.c. fat loss and diabetes), mandibuloacral dys- mice survived embryonic development but died at birth with plasia (skeletal malformations and lipodystrophy), atypical defects in lung and bone. Fibroblasts from mutant embryos grew Werner’s syndrome, and Hutchinson–Gilford progeria syn- under standard cell-culture conditions but displayed grossly mis- drome (precocious aging syndromes) (13–17). Many of the shapen nuclei, impaired differentiation, increased polyploidy, and phenotypes associated with LMNA mutations in humans have premature senescence. Thus, the lamin B1 mutant mice provide been observed in mice harboring Lmna mutations. Mice with evidence for a broad and nonredundant function of lamin B1 in null mutations in the Lmna gene develop muscular dystrophy mammalian development. These mutant mice and cell lines derived (18), peripheral neuropathy (19), and cardiomyopathy (20). from them will be useful models for studying the role of the nuclear Gene-targeted mice with mutations leading to multiple Lmna lamina in various cellular processes. mRNA splicing abnormalities exhibit aging-like phenotypes akin to those observed in humans with progeria, such as reduced nuclear envelope ͉ lamins ͉ knockout mice ͉ gene trapping lifespan, osteolytic lesions of bones, dental abnormalities, and cells with misshapen nuclei (21). A deficiency in Zmpste24 (a he nuclear lamina, a protein meshwork that lines the inner metalloproteinase of the endoplasmic reticulum) prevents the Tnuclear membrane, is critical in fundamental cellular pro- processing of prelamin A to mature lamin A, resulting in the cesses, including nuclear organization, chromatin segregation, accumulation of prelamin A within cells (22, 23). Zmpste24- DNA replication, and gene transcription (1–5). The principal deficient mice exhibit multiple phenotypes reminiscent of prog- eria, including hair loss, dental abnormalities, and osteolysis of protein components of the lamina are lamins, which are mem- the clavicle and other bones. bers of the intermediate filament protein family. Like other Although dozens of disease-causing LMNA mutations have intermediate filament proteins, lamins possess an amino- been catalogued, defects in the B-type lamins have never been terminal head domain and a highly conserved central ␣-rod identified. The absence of human disease suggests that the loss domain for polymerization and oligomerization (6). Lamins are, of one of the B-type lamins is either inconsequential or causes however, distinguished from other intermediate filament pro- death early in development. ‘‘Knockdown’’ experiments with teins by a nuclear localization motif. In addition, prelamin A and small interfering RNAs (siRNAs) favor the latter possibility, lamins B1 and B2 contain a carboxyl-terminal CAAX motif that because reduced lamin B1 expression caused cultured cells to triggers a series of posttranslational modifications (farnesylation, stop growing and undergo apoptosis, whereas reduced expres- endoproteolytic trimming of the last three amino acid residues, sion of the A-type lamins had no appreciable effect on cell and methylation of the newly exposed farnesylcysteine) (6). growth (24). Aside from their structural role in the formation of the nuclear To define the importance of lamin B1 in mammals, we lamina, lamins A and C are found in the nucleoplasm adjacent generated Lmnb1 mutant mice. In view of the aforementioned to sites of DNA synthesis and RNA processing, suggesting that siRNA experiments (24), we predicted that the mutant mice these proteins could influence both DNA replication and gene would die early in embryonic development. To our surprise, expression (2, 7, 8). however, the mice survived until birth, albeit with bone and lung In vertebrates, lamins are classified as A or B type, based on abnormalities. Lamin B1-deficient fibroblasts grew under stan- sequence homology, expression pattern, biochemical properties, and localization during mitosis. The A-type lamins, lamins A and C, are synthesized from alternatively spliced transcripts of This paper was submitted directly (Track II) to the PNAS office. LMNA and are expressed in most differentiated cells (9). Abbreviations: ES, embryonic stem; MEF, mouse embryonic fibroblast; ␤-gal, ␤-galactosi- Somatic cells also express two B-type lamins, lamin B1 and lamin dase; dpc, days post coitus. B2, which are encoded by LMNB1 and LMNB2, respectively. ʈTo whom correspondence should be addressed at: 11301 Wilshire Boulevard, Building 113, Although the A- and B-type lamins interact with an overlapping Room 312, Los Angeles, CA 90073. E-mail: [email protected]. set of other nuclear envelope proteins, they exhibit distinct © 2004 by The National Academy of Sciences of the USA 10428–10433 ͉ PNAS ͉ July 13, 2004 ͉ vol. 101 ͉ no. 28 www.pnas.org͞cgi͞doi͞10.1073͞pnas.0401424101 Downloaded by guest on September 23, 2021 dard culture conditions but exhibited misshapen nuclei and growth and differentiation abnormalities. Thus, lamin B1 is required for normal embryonic development and postnatal survival, but the lamin B1 mutation did not lead to lethality at the cellular level. Materials and Methods An Insertional Mutation in Lmnb1. Mouse embryonic stem (ES) cells containing a gene-trap insertion in Lmnb1 (cell line XA130) were obtained from BayGenomics (San Francisco) (25). Inser- tion of the gene-trap vector into Lmnb1 was verified by direct sequencing of cDNA obtained by 5Ј rapid amplification of cDNA ends (26). Chimeric mice were generated by blastocyst micro- injection and crossed with C57BL͞6J mice to create mice carrying the mutant Lmnb1 allele (Lmnb1ϩ/⌬). Offspring were genotyped by PCR of genomic DNA with primers specific for the wild-type Lmnb1 allele (Lmnb1 forward, 5Ј-TCCGTGTCGT- GTGGTAGGAGG-3Ј; Lmnb1 reverse, 5Ј-GCAGGAGGGTT- GGGAAAGCC-3Ј) and for the mutant allele carrying the gene-trap insertion (Lmnb1 forward, as above; vector reverse, 5Ј-CACTCCAACCTCCGCAAACTC-3Ј). Cell Culture and Western Blots. Primary mouse embryonic fibro- blasts (MEFs) were prepared from embryos harvested 14.5 days post coitus (dpc) (27). Cells were maintained at 37°Cin5%CO2 ͞ with DMEM containing 10% FBS, penicillin streptomycin, and Fig. 1. Structure and expression of lamin B1 in gene-trap mice. (A) Structure 2 mM glutamine. Two days after reaching confluence, adipocyte of lamin B1 in wild-type and Lmnb1⌬/⌬ mice. The amino-terminal half of lamin differentiation was induced by adding insulin, dexamethasone, B1 consists primarily of the rod domain (1A, 1B, 2A, and 2B) and flanking isomethylbutylxanthine, and the peroxisome proliferator acti- phosphorylation sites (P-site). The C-terminal half contains the nuclear local- vated receptor ␥ ligand, rosiglitazone (BRL 49653; a gift from ization signal (NLS) and the CAAX motif. In Lmnb1⌬/⌬ cells, a portion of the rod Todd Leff, Wayne State University, Detroit) (28). Karyotype domain and the entire carboxyl-terminal domain are replaced by ␤geo. (B) analysis was performed after treating cells for5hwith0.1␮g͞ml RT-PCR analysis of mRNA expression levels for lamins B1 (5Ј and 3Ј regions), B2, ϩ/ϩ ϩ/⌬ ⌬/⌬ colcemid (Sigma) (27). For Western blot analysis, cellular pro- A, and C in Lmnb1 , Lmnb1 , and Lmnb1 MEFs from two embryos
Load more

Recommended publications
  • The Treasure Vault Can Be Opened: Large-Scale Genome Skimming Works Well Using Herbarium and Silica Gel Dried Material
    The Treasure Vault Can be Opened: Large-Scale Genome Skimming Works Well Using Herbarium and Silica Gel Dried Material Inger Greve Alsos, Sebastien Lavergne, Marie Kristine Føreid Merkel, Marti Boleda, Youri Lammers, Adriana Alberti, Charles Pouchon, France Denoeud, Iva Pitelkova, Mihai Pușcaș, et al. To cite this version: Inger Greve Alsos, Sebastien Lavergne, Marie Kristine Føreid Merkel, Marti Boleda, Youri Lammers, et al.. The Treasure Vault Can be Opened: Large-Scale Genome Skimming Works Well Using Herbarium and Silica Gel Dried Material. Plants, MDPI, 2020, 9 (4), pp.432. 10.3390/plants9040432. hal- 02612289 HAL Id: hal-02612289 https://hal.archives-ouvertes.fr/hal-02612289 Submitted on 12 Nov 2020 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. Distributed under a Creative Commons Attribution| 4.0 International License plants Article The Treasure Vault Can be Opened: Large-Scale Genome Skimming Works Well Using Herbarium and Silica Gel Dried Material Inger Greve Alsos 1,* , Sebastien Lavergne 2, Marie Kristine Føreid Merkel 1, Marti Boleda 2, Youri Lammers 1, Adriana Alberti 3 , Charles Pouchon 2, France Denoeud 3, Iva Pitelkova 1, 4 2,5 6 2 Mihai Pus, cas, , Cristina Roquet , Bogdan-Iuliu Hurdu , Wilfried Thuiller , Niklaus E.
    [Show full text]
  • The Mystery of the Missing Centriole Solved!
    Downloaded from Carmichael’s Concise Review The Mystery of the Missing Centriole https://www.cambridge.org/core Coming Events Solved! 2018 European Microbiology Research Stephen W. Carmichael* and Jeffery L. Salisbury Conference December 3–5, 2018 Mayo Clinic, Rochester, MN 55905 Valencia, Spain http://europeanmicrobiology.madridge.com *[email protected] From Images to Knowledge with . IP address: ImageJ & Friends December 6–8, 2018 Heidelberg, Germany www.embl.de/training/events/2018/IMJ18-01 Most mammalian cells contain two centrioles that duplicate during cell division. One 170.106.33.19 American Society for Cell Biology would expect the human zygote to have two centrioles during interphase and four centrioles (ASCB) 2018 Annual Meeting during mitosis. However, four centrioles have never been shown in any mammalian zygote, December 8–12, 2018 only three. Since the human oocyte lacks centrioles, it seems the centrioles of the embryo are San Diego, CA paternally inherited. The paternal centrioles reside in the sperm neck, a region at the junction , on http://ascb.org/future-ascb-annual-meetings of the nucleus and flagellum. The neck also contains the striated columns and capitulum, 28 Sep 2021 at 15:40:20 2D Materials and Technologies which surround a relatively clear region called the vault. December 10–13, 2018 Melbourne, Australia The current dogma is that the centrioles in the sperm undergo reduction so that a www.fleet.org.au/icon2dmat sperm cell then contains one typical centriole, called the proximal centriole (PC), while the Smart NanoMaterials 2018: distal centriole (DC) disintegrates and the protein surrounding it is eliminated and replaced Advances, Innovation and Application by the vault.
    [Show full text]
  • Dissertation
    Dissertation submitted to the Combined Faculty of Natural Sciences and Mathematics of the Ruperto-Carola University of Heidelberg, Germany for the degree of Doctor of Natural Sciences Presented by M.Sc. Matilde Bertolini born in Parma, Italy Oral examination: 02/03/2021 Profiling interactions of proximal nascent chains reveals a general co-translational mechanism of protein complex assembly Referees: Prof. Dr. Bernd Bukau Prof. Dr. Caludio Joazeiro Preface Contributions The experiments and analyses presented in this Thesis were conducted by myself unless otherwise indicated, under the supervision of Dr. Günter Kramer and Prof. Dr. Bernd Bukau. The Disome Selective Profiling (DiSP) technology was developed in collaboration with my colleague Kai Fenzl, with whom I also generated initial datasets of human HEK293-T and U2OS cells. Dr. Ilia Kats developed important bioinformatics tools for the analysis of DiSP data, including RiboSeqTools and the sigmoid fitting algorithm. He also offered great input on statistical analyses. Dr. Frank Tippmann performed analysis of crystal structures. Table of Contents TABLE OF CONTENTS List of Figures ......................................................................................................V List of Tables ...................................................................................................... VII List of Equations .............................................................................................. VIII Abbreviations ....................................................................................................
    [Show full text]
  • Regulation, Evolution and Consequences of Cotranslational
    Available online at www.sciencedirect.com ScienceDirect Regulation, evolution and consequences of cotranslational protein complex assembly 1 2 3 Eviatar Natan , Jonathan N Wells , Sarah A Teichmann and 2 Joseph A Marsh Most proteins assemble into complexes, which are involved in evolution, most prokaryotic complexes are homomers, almost all cellular processes. Thus it is crucial for cell viability while most eukaryotic complexes are heteromers [5–7]. that mechanisms for correct assembly exist. The timing of assembly plays a key role in determining the fate of the protein: Protein complexes are crucial for a large number of biolog- if the protein is allowed to diffuse into the crowded cellular ical functions, and different types of protein quaternary milieu, it runs the risk of forming non-specific interactions, structures have been shown to facilitate different biological potentially leading to aggregation or other deleterious functions and allosteric regulation [8 ,9–12]. A large num- outcomes. It is therefore expected that strong regulatory ber of other benefits have been proposed [4 ,13]. For mechanisms should exist to ensure efficient assembly. In this example, considering the possibility of acquiring mutations review we discuss the cotranslational assembly of protein during transcription and translation, it is more efficient to complexes and discuss how it occurs, ways in which it is synthesize a larger structure in modules of subunits. Im- regulated, potential disadvantages of cotranslational portantly, it also allows fine spatial and temporal regulation, interactions between proteins and the implications for the and reduces folding complexity in forming unique shapes inheritance of dominant-negative genetic disorders. such rings or filaments.
    [Show full text]
  • Identification of DNAH6 Mutations in Infertile Men with Multiple
    www.nature.com/scientificreports OPEN Identifcation of DNAH6 mutations in infertile men with multiple morphological abnormalities of the sperm fagella Chaofeng Tu1,2,3,4, Hongchuan Nie1,2,3,4, Lanlan Meng2, Shimin Yuan2, Wenbin He1,2,3, Aixiang Luo1, Haiyu Li1, Wen Li1,2,3, Juan Du1,2,3, Guangxiu Lu1,2,3, Ge Lin1,2,3 & Yue-Qiu Tan1,2,3* Male infertility due to spermatogenesis defects afects millions of men worldwide. However, the genetic etiology of the vast majority remains unclear. Here we describe three men with primary infertility due to multiple morphological abnormalities of the sperm fagella (MMAF) from two unrelated Han Chinese families. We performed whole-exome sequencing (WES) and Sanger sequencing on the proband of family 1, and found that he carried novel compound heterozygous missense mutations in dynein axonemal heavy chain 6 (DNAH6) that resulted in the substitution of a conserved amino acid residue and co-segregated with the MMAF phenotype in this family. Papanicolaou staining and transmission electron microscopy analysis revealed morphological and ultrastructural abnormalities in the sperm fagella in carriers of these genetic variants. Immunostaining experiments showed that DNAH6 was localized in the sperm tail. This is the frst report identifying novel recessive mutations in DNAH6 as a cause of MMAF. These fndings expand the spectrum of known MMAF mutations and phenotypes and provide information that can be useful for genetic and reproductive counseling of MMAF patients. Infertility is a major health concern that afects more than 20 million men worldwide1. Factors contributing to male infertility include genetic disorders, urogenital infections, and immunological or hormonal abnormalities.
    [Show full text]
  • The Transformation of the Centrosome Into the Basal Body: Similarities and Dissimilarities Between Somatic and Male Germ Cells and Their Relevance for Male Fertility
    cells Review The Transformation of the Centrosome into the Basal Body: Similarities and Dissimilarities between Somatic and Male Germ Cells and Their Relevance for Male Fertility Constanza Tapia Contreras and Sigrid Hoyer-Fender * Göttingen Center of Molecular Biosciences, Johann-Friedrich-Blumenbach Institute for Zoology and Anthropology-Developmental Biology, Faculty of Biology and Psychology, Georg-August University of Göttingen, 37077 Göttingen, Germany; [email protected] * Correspondence: [email protected] Abstract: The sperm flagellum is essential for the transport of the genetic material toward the oocyte and thus the transmission of the genetic information to the next generation. During the haploid phase of spermatogenesis, i.e., spermiogenesis, a morphological and molecular restructuring of the male germ cell, the round spermatid, takes place that includes the silencing and compaction of the nucleus, the formation of the acrosomal vesicle from the Golgi apparatus, the formation of the sperm tail, and, finally, the shedding of excessive cytoplasm. Sperm tail formation starts in the round spermatid stage when the pair of centrioles moves toward the posterior pole of the nucleus. The sperm tail, eventually, becomes located opposed to the acrosomal vesicle, which develops at the anterior pole of the nucleus. The centriole pair tightly attaches to the nucleus, forming a nuclear membrane indentation. An Citation: Tapia Contreras, C.; articular structure is formed around the centriole pair known as the connecting piece, situated in the Hoyer-Fender, S. The Transformation neck region and linking the sperm head to the tail, also named the head-to-tail coupling apparatus or, of the Centrosome into the Basal in short, HTCA.
    [Show full text]
  • AP Biology Life’S Beginning on Earth According to Scientific Findings (Associated Learning Objectives: 1.9, 1.10, 1.11, 1.12, 1.27, 1.28, 1.29, 1.30, 1.31, and 1.32)
    AP Auburn University AP Summer Institute BIOLOGYJuly 11-14, 2016 AP Biology Life’s beginning on Earth according to scientific findings (Associated Learning Objectives: 1.9, 1.10, 1.11, 1.12, 1.27, 1.28, 1.29, 1.30, 1.31, and 1.32) I. The four steps necessary for life to emerge on Earth. (This is according to accepted scientific evidence.) A. First: An abiotic (non-living) synthesis of Amino Acids and Nucleic Acids must occur. 1. The RNA molecule is believed to have evolved first. It is not as molecularly stable as DNA though. 2. The Nucleic Acids (DNA or RNA) are essential for storing, retrieving, or conveying by inheritance molecular information on constructing the components of living cells.. 3. The Amino Acids, the building blocks of proteins, are needed to construct the “work horse” molecules of a cell. a. The majority of a cell or organism, in biomass (dry weight of an organism), is mostly protein. B. Second: Monomers must be able to join together to form more complex polymers using energy that is obtained from the surrounding environment. 1. Seen in monosaccharides (simple sugars) making polysaccharides (For energy storage or cell walls of plants.) 2. Seen in the making of phospholipids for cell membranes. 3. Seen in the making of messenger RNA used in making proteins using Amino Acids. 4. Seen in making chromosomes out of strings of DNA molecules. (For information storage.) C. Third: The RNA/DNA molecules form and gain the ability to reproduce and stabilize by using chemical bonds and complimentary bonding.
    [Show full text]
  • Identification and Functional Activation of Peroxisome Proliferator-Activated Receptor in Human Upper Aerodigestive Cancer
    Identification and Functional Activation of Peroxisome Proliferator-Activated Receptor in Human Upper Aerodigestive Cancer A DISSERTATION SUBMITTED TO THE FACULTY OF THE GRADUATE SCHOOL OF THE UNIVERSITY OF MINNESOTA BY Simon K. Wright, MD IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY Frank G. Ondrey, MD., Ph.D November 2012 © Simon K. Wright, MD, 2012 Acknowledgements Supported by NCI/NIH P30 CA77598-07 Cancer Center Support Grant (FGO), The Translational Biomarkers Initiative and other funding from the Lions 5M Foundation (FGO), Iowa Health Systems Research Grant (SKW) and American Cancer Society Institutional Research Grant IRG-58-001-40IRG44 (PMG). i Abstract Squamous cell carcinoma of the head and neck (SCCHN) is an aggressive malignancy whose carcinogenesis occurs in multiple stages years to decades after carcinogen exposure. In spite of continued advances in the understanding of molecular biology of SCCHN and the introduction of a multitude of multi-modality treatment protocols, the 20-50% survival of stage III and IV disease has not changed appreciably in over twenty years. Efforts to treat or prevent recurrence have predominantly involved the use of cytotoxic chemotherapy, however the use of retinoids as a chemoprevention agent has been clinically assessed. Success has been limited by toxicity of retinoids and reversal of differentiation changes upon cessation of treatment. Peroxisome proliferator-activated receptors (PPARs) are lipid-activated transcription factors belonging to the steroid/thyroid/retinoic acid nuclear receptor superfamily. PPARs primarily target genes involved in lipid homeostasis; one isoform, PPARγ, directs the differentiation of precursor cells into adipocytes. PPARγ heterodimerizes with RXRα to form a functional transcription factor.
    [Show full text]
  • Characterization of the Sea Urchin Major Vault Protein (SU-MVP)
    DEVELOPMENTAL BIOLOGY 190, 117±128 (1997) ARTICLE NO. DB978676 Characterization of the Sea Urchin ViewMajor metadata, citation Vault and similar Protein: papers at core.ac.uk A Possible Role brought to you by CORE for Vault Ribonucleoprotein Particles provided by Elsevier - Publisher Connector in Nucleocytoplasmic Transport Danielle R. Hamill and Kathy A. Suprenant Department of Biochemistry, Cell and Molecular Biology, University of Kansas, Lawrence, Kansas 66045 Vaults are large ribonucleoprotein particles that have been identi®ed in a wide range of eukaryotic organisms. Although present in thousands of copies per cell, their function remains unknown. In this report, we identify the major vault protein in sea urchins as a 107-kDa polypeptide that copuri®es with microtubules and ribosomes. Although initially identi®ed in microtubule preparations, the sea urchin major vault protein is not predominantly microtubule-associated in vivo. Rather, the sea urchin major vault protein is present throughout the cytoplasm in eggs and embryos and in the nucleus in adult somatic cells. Within the nucleus, the sea urchin major vault protein is concentrated in the region of the nucleolus and to punctate regions of the nuclear envelope. In addition, the vault protein localizes to short linear strings juxtaposed to the exterior of the nucleus and extending outward into the cytoplasm. Based on their copuri®cation and intracellular distribution, vaults may be involved in the nucleocytoplasmic transport of ribosomes and/or mRNA. q 1997 Academic Press INTRODUCTION coincident with, and clustered at, the distal ends of actin stress ®bers (Kedersha and Rome, 1990). Vault immunoreac- A vault is a large ribonucleoprotein (RNP) particle nearly tivity appears to be excluded from the nucleus (Kedersha three times the size of a ribosome and 10-fold larger than and Rome, 1990).
    [Show full text]
  • Protein Synthesis Worksheet Living Environment Answer Key
    Protein Synthesis Worksheet Living Environment Answer Key certitudes.Mineral Llewellyn Rodolphe sometimes is necessarian phase hisand Confucianist cobble solitarily yonder while and convexo-convex cames so technically! Osborn Niki unmew still qualifyingand besought. laughingly while brumal Daniel flurries that For growth and water content, effort to catalyze the synthesis worksheet living environment answer key is a loading icon above the activation of time to its contents Base your answers to questions 2 through 6 on these the information and data attribute below and erode your. Knote J Regents Living Environment Powerpoint Notes. My friends are much shorter and functions within that broad theme of replicating while some examples. What was excellent first house form? Protein Synthesis Worksheet Name an Environment Mr Buckley Living Environment Mr Buckley This. Lesson Goals Students will remain the parts and functions of a gift as they money to reproduction in plants. Many cloned organisms exhibit a higher rate of genetic disorders and health problems. Though exceptions to or variations on the code exist, a need two create a console account. The groom of office cell is carried out being the many difassembles, for practical purposes, are made what many cells. Draw a vault of an enzyme putting two substrates together. Part D Multiple civil and short answer pertaining to the 4 NYS labs. Some proteins are key. Now, where influence of humans on other organisms occurs through voluntary use and pollution. Rather than their environments and proteins can you answer key. Fluid Mosaic Model Two layers of phospholipid molecules form the lipid bilayer of top cell membrane.
    [Show full text]
  • RNA Metabolism Guided by RNA Modifications
    biomolecules Review RNA Metabolism Guided by RNA Modifications: The Role of SMUG1 in rRNA Quality Control Lisa Lirussi 1,2 , Özlem Demir 3, Panpan You 1,2, Antonio Sarno 4,5 , Rommie E. Amaro 3 and Hilde Nilsen 1,2,* 1 Department of Clinical Molecular Biology, University of Oslo, 0318 Oslo, Norway; [email protected] (L.L.); [email protected] (P.Y.) 2 Department of Clinical Molecular Biology (EpiGen), Akershus University Hospital, 1478 Lørenskog, Norway 3 Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093, USA; [email protected] (Ö.D.); [email protected] (R.E.A.) 4 Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, NTNU, NO-7491 Trondheim, Norway; [email protected] 5 SINTEF Ocean AS, 7010 Trondheim, Norway * Correspondence: [email protected]; Tel.: +47-67963922 Abstract: RNA modifications are essential for proper RNA processing, quality control, and matura- tion steps. In the last decade, some eukaryotic DNA repair enzymes have been shown to have an ability to recognize and process modified RNA substrates and thereby contribute to RNA surveil- lance. Single-strand-selective monofunctional uracil-DNA glycosylase 1 (SMUG1) is a base excision repair enzyme that not only recognizes and removes uracil and oxidized pyrimidines from DNA but is also able to process modified RNA substrates. SMUG1 interacts with the pseudouridine synthase dyskerin (DKC1), an enzyme essential for the correct assembly of small nucleolar ribonucle- oproteins (snRNPs) and ribosomal RNA (rRNA) processing. Here, we review rRNA modifications and RNA quality control mechanisms in general and discuss the specific function of SMUG1 in rRNA metabolism.
    [Show full text]
  • Origin of Microcells in the Human Sarcoma Cell Line HT-1080
    73 Origin of microcells in the human sarcoma cell line HT-1080 Indulis Bui¸kis, L¯ıga Harju and numbers of microcells in tumour tissue markedly in- Talivaldis¯ Freivalds ∗ crease after chemotherapy, irradiation or immunother- Latvian Institute of Experimental and Clinical apy. Medicine, R¯ıga, LV-1004, Latvia Various ideas have been proposed for the origin of the microcells. Microcells in tumour tissue have been Received 17 July 1998 attributed to host immunocompetetive cell (macro- Revised 5 January 1999 phage progenitors, lymphocytes, etc.) and migration Accepted 17 February 1999 from blood capillaries into tumour tissue [21,24,48]. Other authors have considered microcells to origi- The aim of this study was to investigate the development nate from large damaged tumour cells undergoing of microcells in the human sarcoma cell line HT-1080 af- programmed cell death (apoptosis) [20,41]. Apop- ter interference with thiophosphamidum. We found that dam- totic events are manifested by tumour cell shrink- aged interphase macrocells located at the projection of the age, nucleus condensation and fragmentation, inter- nucleolus may form one or several microcells. The micronu- nucleosomal DNA cleavage and formation of apop- clei of the microcells intensively incorporate the thymidine 0 tic bodies (microcells) with low DNA content [6,16, analogue 5-bromo-2 -deoxyuridine and strongly express ar- 28,52]. Evidence also suggests that hypodiploid mi- gyrophilic nucleolar organiser region proteins. At an early crocells develop from large tumour cells by multipo- phase of the development, the micronuclei contain frag- mented DNA, but in subsequent phases, the micronuclei ac- lar mitosis [14] or by segregation of chromosomes in cumulate polymeric DNA, simultaneously with an increase metaphase – blocked cytogenesis [29].
    [Show full text]