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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. -
Parallel Next Generation Sequencing of DNA and RNA from a Single
www.nature.com/scientificreports OPEN Towards Improving Embryo Prioritization: Parallel Next Generation Sequencing of DNA and Received: 2 August 2018 Accepted: 14 January 2019 RNA from a Single Trophectoderm Published: xx xx xxxx Biopsy Noga Fuchs Weizman1, Brandon A. Wyse1, Ran Antes1, Zenon Ibarrientos1, Mugundhine Sangaralingam1, Gelareh Motamedi1, Valeriy Kuznyetsov1, Svetlana Madjunkova1 & Cliford L. Librach1,2,3,4 Improved embryo prioritization is crucial in optimizing the results in assisted reproduction, especially in light of increasing utilization of elective single embryo transfers. Embryo prioritization is currently based on morphological criteria and in some cases incorporates preimplantation genetic testing for aneuploidy (PGT-A). Recent technological advances have enabled parallel genomic and transcriptomic assessment of a single cell. Adding transcriptomic analysis to PGT-A holds promise for better understanding early embryonic development and implantation, and for enhancing available embryo prioritization tools. Our aim was to develop a platform for parallel genomic and transcriptomic sequencing of a single trophectoderm (TE) biopsy, that could later be correlated with clinical outcomes. Twenty-fve embryos donated for research were utilized; eight for initial development and optimization of our method, and seventeen to demonstrate clinical safety and reproducibility of this method. Our method achieved 100% concordance for ploidy status with that achieved by the classic PGT-A. All sequencing data exceeded quality control metrics. Transcriptomic sequencing data was sufcient for performing diferential expression (DE) analysis. All biopsies expressed specifc TE markers, further validating the accuracy of our method. Using PCA, samples clustered in euploid and aneuploid aggregates, highlighting the importance of controlling for ploidy in every transcriptomic assessment. -
![Solution Structure of the GUCT Domain from Human RNA Helicase II/Gu[Beta]](https://docslib.b-cdn.net/cover/1277/solution-structure-of-the-guct-domain-from-human-rna-helicase-ii-gu-beta-371277.webp)
Solution Structure of the GUCT Domain from Human RNA Helicase II/Gu[Beta]
proteins STRUCTURE O FUNCTION O BIOINFORMATICS Solution structure of the GUCT domain from human RNA helicase II/Gub reveals the RRM fold, but implausible RNA interactions Satoshi Ohnishi,1 Kimmo Pa¨a¨kko¨nen,1 Seizo Koshiba,1 Naoya Tochio,1 Manami Sato,1 Naohiro Kobayashi,1 Takushi Harada,1 Satoru Watanabe,1 Yutaka Muto,1 Peter Gu¨ntert,1 Akiko Tanaka,1 Takanori Kigawa,1,2 and Shigeyuki Yokoyama1,3* 1 Systems and Structural Biology Center, RIKEN, Tsurumi, Yokohama 230-0045, Japan 2 Department of Computational Intelligence and Systems Science, Interdisciplinary Graduate School of Science and Engineering, Tokyo Institute of Technology, Midori-ku, Yokohama 226-8503, Japan 3 Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan INTRODUCTION ABSTRACT a a a a Human RNA helicase II/Gu (RH-II/Gu or Deadbox Human RNA helicase II/Gu (RH-II/Gu ) and RNA helicase protein 21) is a multifunctional enzyme that unwinds dou- II/Gub (RH-II/Gub) are paralogues that share the same ble-stranded RNA in the 50 to 30 direction and folds single- domain structure, consisting of the DEAD box helicase 1–5 domain (DEAD), the helicase conserved C-terminal domain stranded RNA in an ATP-dependent manner. These (helicase_C), and the GUCT domain. The N-terminal regions RNA-unwinding and RNA-folding activities are independ- of the RH-II/Gu proteins, including the DEAD domain and ent, and they reside in distinct regions of the protein. The the helicase_C domain, unwind double-stranded RNAs. The RNA helicase activity is catalyzed by the N-terminal three- 1 C-terminal tail of RH-II/Gua, which follows the GUCT do- quarters of the molecule in the presence of Mg2 , where as main, folds a single RNA strand, while that of RH-II/Gub the RNA-foldase activity is located in the C-terminal region 1 does not, and the GUCT domain is not essential for either and functions in a Mg2 independent manner.2 As shown the RNA helicase or foldase activity. -
Integrating Single-Step GWAS and Bipartite Networks Reconstruction Provides Novel Insights Into Yearling Weight and Carcass Traits in Hanwoo Beef Cattle
animals Article Integrating Single-Step GWAS and Bipartite Networks Reconstruction Provides Novel Insights into Yearling Weight and Carcass Traits in Hanwoo Beef Cattle Masoumeh Naserkheil 1 , Abolfazl Bahrami 1 , Deukhwan Lee 2,* and Hossein Mehrban 3 1 Department of Animal Science, University College of Agriculture and Natural Resources, University of Tehran, Karaj 77871-31587, Iran; [email protected] (M.N.); [email protected] (A.B.) 2 Department of Animal Life and Environment Sciences, Hankyong National University, Jungang-ro 327, Anseong-si, Gyeonggi-do 17579, Korea 3 Department of Animal Science, Shahrekord University, Shahrekord 88186-34141, Iran; [email protected] * Correspondence: [email protected]; Tel.: +82-31-670-5091 Received: 25 August 2020; Accepted: 6 October 2020; Published: 9 October 2020 Simple Summary: Hanwoo is an indigenous cattle breed in Korea and popular for meat production owing to its rapid growth and high-quality meat. Its yearling weight and carcass traits (backfat thickness, carcass weight, eye muscle area, and marbling score) are economically important for the selection of young and proven bulls. In recent decades, the advent of high throughput genotyping technologies has made it possible to perform genome-wide association studies (GWAS) for the detection of genomic regions associated with traits of economic interest in different species. In this study, we conducted a weighted single-step genome-wide association study which combines all genotypes, phenotypes and pedigree data in one step (ssGBLUP). It allows for the use of all SNPs simultaneously along with all phenotypes from genotyped and ungenotyped animals. Our results revealed 33 relevant genomic regions related to the traits of interest. -
DDX47 Polyclonal Antibody
PRODUCT DATA SHEET Bioworld Technology,Inc. DDX47 polyclonal antibody Catalog: BS71653 Host: Rabbit Reactivity: Human,Mouse,Rat BackGround: munogen and the purity is > 95% (by SDS-PAGE). This gene encodes a member of the DEAD box protein Applications: family. DEAD box proteins, characterized by the con- WB 1:500 - 1:2000 served motif Asp-Glu-Ala-Asp (DEAD), are putative IHC 1:50 - 1:200 RNA helicases. They are implicated in a number of cellu- Storage&Stability: lar processes involving alteration of RNA secondary Store at 4°C short term. Aliquot and store at -20°C long structure, such as translation initiation, nuclear and mito- term. Avoid freeze-thaw cycles. chondrial splicing, and ribosome and spliceosome assem- Specificity: bly. Based on their distribution patterns, some members DDX47 polyclonal antibody detects endogenous levels of of this family are believed to be involved in embryogene- DDX47 protein. sis, spermatogenesis, and cellular growth and division. DATA: The protein encoded by this gene can shuttle between the nucleus and the cytoplasm, and has an RNA-independent ATPase activity. Two alternatively spliced transcript var- iants encoding distinct isoforms have been found for this gene. Product: Rabbit IgG, 1mg/ml in PBS with 0.02% sodium azide, 50% glycerol, pH7.2 Western blot analysis of extracts of various cell lines, using DDX47 an- Molecular Weight: tibody. ~ 50 kDa Note: Swiss-Prot: For research use only, not for use in diagnostic procedure. Q9H0S4 Purification&Purity: The antibody was affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific im- Bioworld Technology, Inc. Bioworld technology, co. Ltd. -
An Adipocyte-Specific Lncrap2 - Igf2bp2 Complex Enhances Adipogenesis and Energy Expenditure by Stabilizing Target Mrnas
bioRxiv preprint doi: https://doi.org/10.1101/2020.09.29.318980; this version posted September 29, 2020. 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-NC-ND 4.0 International license. An adipocyte-specific lncRAP2 - Igf2bp2 complex enhances adipogenesis and energy expenditure by stabilizing target mRNAs Juan R. Alvarez-Dominguez1,4, Sally Winther2, Jacob B. Hansen2, Harvey F. Lodish1,3,* and Marko Knoll1,5,* 1 Whitehead Institute for Biomedical Research, 455 Main Street, Cambridge, MA 02142, USA 2 Department of Biology, University of Copenhagen, Universitetsparken 13, DK-2100 Copenhagen, Denmark 3 Departments of Biology and Biological Engineering, Massachusetts Institute of Technology, 21 Ames Street, Cambridge, MA, 02142, USA 4 Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA 5 Institute for Diabetes Research, Helmholtz Zentrum München, Heidemannstrasse 1, 80939 München, Germany *correspondence: [email protected], [email protected] bioRxiv preprint doi: https://doi.org/10.1101/2020.09.29.318980; this version posted September 29, 2020. 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-NC-ND 4.0 International license. Abstract lncRAP2 is a conserved cytoplasmic adipocyte-specific lncRNA required for adipogenesis. Using hybridization-based purification combined with in vivo interactome analyses, we show that lncRAP2 forms ribonucleoprotein complexes with several mRNA stability and translation modulators, among them Igf2bp2. -
Nucleolin and Its Role in Ribosomal Biogenesis
NUCLEOLIN: A NUCLEOLAR RNA-BINDING PROTEIN INVOLVED IN RIBOSOME BIOGENESIS Inaugural-Dissertation zur Erlangung des Doktorgrades der Mathematisch-Naturwissenschaftlichen Fakultät der Heinrich-Heine-Universität Düsseldorf vorgelegt von Julia Fremerey aus Hamburg Düsseldorf, April 2016 2 Gedruckt mit der Genehmigung der Mathematisch-Naturwissenschaftlichen Fakultät der Heinrich-Heine-Universität Düsseldorf Referent: Prof. Dr. A. Borkhardt Korreferent: Prof. Dr. H. Schwender Tag der mündlichen Prüfung: 20.07.2016 3 Die vorgelegte Arbeit wurde von Juli 2012 bis März 2016 in der Klinik für Kinder- Onkologie, -Hämatologie und Klinische Immunologie des Universitätsklinikums Düsseldorf unter Anleitung von Prof. Dr. A. Borkhardt und in Kooperation mit dem ‚Laboratory of RNA Molecular Biology‘ an der Rockefeller Universität unter Anleitung von Prof. Dr. T. Tuschl angefertigt. 4 Dedicated to my family TABLE OF CONTENTS 5 TABLE OF CONTENTS TABLE OF CONTENTS ............................................................................................... 5 LIST OF FIGURES ......................................................................................................10 LIST OF TABLES .......................................................................................................12 ABBREVIATION .........................................................................................................13 ABSTRACT ................................................................................................................19 ZUSAMMENFASSUNG -
Structural and Biochemical Studies of the Human DEAD-Box Helicase Dbp5 and Nucleoporin Nup214 Involved in Mrna Export‟ (Grade: 1.0) Since Sep
Dissertation zur Erlangung des Doktorgrades der Fakultät für Chemie und Pharmazie der Ludwig-Maximilians-Universität München Structural and Biochemical Studies of the Human DEAD-box Helicase Dbp5 and Nucleoporin Nup214 Involved in mRNA Export Holger von Moeller aus Leverkusen 2009 Erklärung Diese Dissertation wurde im Sinne von §13 Abs. 3 der Promotionsordnung vom 29. Januar 1998 von Frau Prof. Dr. Elena Conti betreut. Ehrenwörtliche Versicherung Diese Dissertation wurde selbständig, ohne unerlaubte Hilfe erarbeitet. München, am 28.05.2009 Holger von Moeller Dissertation eingereicht am: 29.05.2009 1. Gutachter Prof. Dr. Elena Conti 2. Gutachter Prof. Dr. Patrick Cramer Mündliche Prüfung am: 30.09.2009 Meinen Eltern Abstract The hallmark of eukaryotic evolution was the development of the nucleus in cells. This compartmentalization requires the nucleocytoplasmic transport of thousands of molecules. The gate into and out of the nucleus is the nuclear pore complex (NPC). One of the molecules that needs to be exported from the nucleus is messenger RNA (mRNA). mRNA associates with proteins in the nucleus forming a messenger ribonucleoprotein particle (mRNP). mRNPs bind to dedicated transport factors that facilitate movement through the NPC. One protein that associates to mRNPs is the helicase Dbp5, which belongs to the DEAD-box family of RNA helicases. Dbp5 is essential for mRNA export in both yeast and humans. It binds RNA and is concentrated and locally activated at the cytoplasmic side of the nuclear pore complex, where it interacts with the cytoplasmic nucleoporin Nup214. In my PhD work, I have determined the crystal structures of human Dbp5 bound to RNA and AMPPNP, and bound to Nup214. -
2020 Program Book
PROGRAM BOOK Note that TAGC was cancelled and held online with a different schedule and program. This document serves as a record of the original program designed for the in-person meeting. April 22–26, 2020 Gaylord National Resort & Convention Center Metro Washington, DC TABLE OF CONTENTS About the GSA ........................................................................................................................................................ 3 Conference Organizers ...........................................................................................................................................4 General Information ...............................................................................................................................................7 Mobile App ....................................................................................................................................................7 Registration, Badges, and Pre-ordered T-shirts .............................................................................................7 Oral Presenters: Speaker Ready Room - Camellia 4.......................................................................................7 Poster Sessions and Exhibits - Prince George’s Exhibition Hall ......................................................................7 GSA Central - Booth 520 ................................................................................................................................8 Internet Access ..............................................................................................................................................8 -
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. -
R-Loop Proximity Proteomics Identifies a Role of DDX41 in Transcription- 2 Associated Genomic Instability
R-loop proximity proteomics identies a role of DDX41 in transcription-associated genomic instability Thorsten Mosler Institute of Molecular Biology (IMB) Francesca Conte Institute of Molecular Biology (IMB) Ivan Mikicic Institute of Molecular Biology (IMB) https://orcid.org/0000-0003-3393-0688 Nastasja Kreim Institute of Molecular Biology Martin Möckel Institute of Molecular Biology (IMB) Johanna Flach Medical Faculty Mannheim of the Heidelberg University Brian Luke Johannes Gutenberg University of Mainz https://orcid.org/0000-0002-1648-5511 Petra Beli ( [email protected] ) Institute of Molecular Biology (IMB) https://orcid.org/0000-0001-9507-9820 Article Keywords: DDX41, genomic instability, proximity proteomics, R-loops, transcription Posted Date: April 26th, 2021 DOI: https://doi.org/10.21203/rs.3.rs-337351/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License 1 R-loop proximity proteomics identifies a role of DDX41 in transcription- 2 associated genomic instability 1 1 1 1 1 3 Thorsten Mosler , Francesca Conte , Ivan Mikicic , Nastasja Kreim , Martin M. Möckel , 4 Johanna Flach2, Brian Luke1,3, Petra Beli1,3,# 5 6 1Institute of Molecular Biology (IMB), Mainz, Germany 7 2Department of Hematology and Oncology, Medical Faculty Mannheim of the Heidelberg 8 University, Mannheim, Germany 9 3Institute of Developmental Biology and Neurobiology (IDN), Johannes Gutenberg-Universität, 10 Mainz, Germany. 11 #Correspondence should be addressed to [email protected] 12 13 14 15 16 17 18 19 20 21 22 Keywords: DDX41, genomic instability, proximity proteomics, R-loops, transcription 23 1 24 Abstract 25 Transcription can pose a threat to genomic stability through the formation of R-loops that 26 obstruct the progression of replication forks. -
Long First Exons and Epigenetic Marks Distinguish Conserved Pachytene
ARTICLE https://doi.org/10.1038/s41467-020-20345-3 OPEN Long first exons and epigenetic marks distinguish conserved pachytene piRNA clusters from other mammalian genes ✉ Tianxiong Yu 1,2,7, Kaili Fan 1,2,7, Deniz M. Özata 3, Gen Zhang4,YuFu 2,5,6, William E. Theurkauf4 , ✉ ✉ Phillip D. Zamore 3 & Zhiping Weng 1,2 – 1234567890():,; In the male germ cells of placental mammals, 26 30-nt-long PIWI-interacting RNAs (piR- NAs) emerge when spermatocytes enter the pachytene phase of meiosis. In mice, pachytene piRNAs derive from ~100 discrete autosomal loci that produce canonical RNA polymerase II transcripts. These piRNA clusters bear 5′ caps and 3′ poly(A) tails, and often contain introns that are removed before nuclear export and processing into piRNAs. What marks pachytene piRNA clusters to produce piRNAs, and what confines their expression to the germline? We report that an unusually long first exon (≥ 10 kb) or a long, unspliced transcript correlates with germline-specific transcription and piRNA production. Our integrative analysis of tran- scriptome, piRNA, and epigenome datasets across multiple species reveals that a long first exon is an evolutionarily conserved feature of pachytene piRNA clusters. Furthermore, a highly methylated promoter, often containing a low or intermediate level of CG dinucleotides, correlates with germline expression and somatic silencing of pachytene piRNA clusters. Pachytene piRNA precursor transcripts bind THOC1 and THOC2, THO complex subunits known to promote transcriptional elongation and mRNA nuclear export. Together, these features may explain why the major sources of pachytene piRNA clusters specifically gen- erate these unique small RNAs in the male germline of placental mammals.