Reverse Transcriptase Genes Are Highly Abundant and Transcriptionally Active in Marine Plankton Assemblages
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Two Independent Retrons with Highly Diverse Reverse Transcriptases In
Proc. Natl. Acad. Sci. USA Vol. 87, pp. 942-945, February 1990 Biochemistry Two independent retrons with highly diverse reverse transcriptases in Myxococcus xanthus (multicopy single-stranded DNA/2',5'-phosphodiester/codon usage/myxobacteria) SUMIKO INOUYE, PETER J. HERZER, AND MASAYORI INOUYE Department of Biochemistry, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ 08854 Communicated by Russell F. Doolittle, November 27, 1989 (received for review September 29, 1989) ABSTRACT A reverse transcriptase (RT) was recently found that the Mx65 retron is highly diverse and independent found in Myxococcus xanthus, a Gram-negative soil bacterium. from the Mx162 retron and that RT associated with the Mx65 This RT has been shown to be associated with a chromosomal retron has only 47% identity with RT for the Mx162 retron. region designated a retron responsible for the synthesis of a peculiar extrachromosomal DNA called msDNA (multicopy single-stranded DNA). We demonstrate that M. xanthus con- MATERIALS AND METHODS tains two independent, unlinked retrons, one for the synthesis Materials. The clone of the 9.0-kilobase (kb) Pst I fragment of msDNA-Mxl62 and the other for msDNA-Mx65. The struc- containing the Mx65 retron was obtained (8). Restriction tural analysis of the retron for msDNA-Mx65 revealed that the enzymes were purchased from New England Biolabs and coding regions for msdRNA (msr) and msDNA (msd), and an Boehringer Mannheim. open reading frame (ORF) downstream of msr are arranged in A deletion mutant strain ofthe Mx162 retron, AmsSX, was the same manner as found for the Mx162 retron. -
RNA-Based Technologies for Engineering Plant Virus Resistance
plants Review RNA-Based Technologies for Engineering Plant Virus Resistance Michael Taliansky 1,2,*, Viktoria Samarskaya 1, Sergey K. Zavriev 1 , Igor Fesenko 1 , Natalia O. Kalinina 1,3 and Andrew J. Love 2,* 1 Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, 117997 Moscow, Russia; [email protected] (V.S.); [email protected] (S.K.Z.); [email protected] (I.F.); [email protected] (N.O.K.) 2 The James Hutton Institute, Invergowrie, Dundee DD2 5DA, UK 3 Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Leninskie Gory, 119991 Moscow, Russia * Correspondence: [email protected] (M.T.); [email protected] (A.J.L.) Abstract: In recent years, non-coding RNAs (ncRNAs) have gained unprecedented attention as new and crucial players in the regulation of numerous cellular processes and disease responses. In this review, we describe how diverse ncRNAs, including both small RNAs and long ncRNAs, may be used to engineer resistance against plant viruses. We discuss how double-stranded RNAs and small RNAs, such as artificial microRNAs and trans-acting small interfering RNAs, either produced in transgenic plants or delivered exogenously to non-transgenic plants, may constitute powerful RNA interference (RNAi)-based technology that can be exploited to control plant viruses. Additionally, we describe how RNA guided CRISPR-CAS gene-editing systems have been deployed to inhibit plant virus infections, and we provide a comparative analysis of RNAi approaches and CRISPR-Cas technology. The two main strategies for engineering virus resistance are also discussed, including direct targeting of viral DNA or RNA, or inactivation of plant host susceptibility genes. -
REVIEW ARTICLE the Genetics of Autism
REVIEW ARTICLE The Genetics of Autism Rebecca Muhle, BA*; Stephanie V. Trentacoste, BA*; and Isabelle Rapin, MD‡ ABSTRACT. Autism is a complex, behaviorally de- tribution of a few well characterized X-linked disorders, fined, static disorder of the immature brain that is of male-to-male transmission in a number of families rules great concern to the practicing pediatrician because of an out X-linkage as the prevailing mode of inheritance. The astonishing 556% reported increase in pediatric preva- recurrence rate in siblings of affected children is ϳ2% to lence between 1991 and 1997, to a prevalence higher than 8%, much higher than the prevalence rate in the general that of spina bifida, cancer, or Down syndrome. This population but much lower than in single-gene diseases. jump is probably attributable to heightened awareness Twin studies reported 60% concordance for classic au- and changing diagnostic criteria rather than to new en- tism in monozygotic (MZ) twins versus 0 in dizygotic vironmental influences. Autism is not a disease but a (DZ) twins, the higher MZ concordance attesting to ge- syndrome with multiple nongenetic and genetic causes. netic inheritance as the predominant causative agent. By autism (the autistic spectrum disorders [ASDs]), we Reevaluation for a broader autistic phenotype that in- mean the wide spectrum of developmental disorders cluded communication and social disorders increased characterized by impairments in 3 behavioral domains: 1) concordance remarkably from 60% to 92% in MZ twins social interaction; 2) language, communication, and and from 0% to 10% in DZ pairs. This suggests that imaginative play; and 3) range of interests and activities. -
(12) Patent Application Publication (10) Pub. No.: US 2016/0289762 A1 KOH Et Al
US 201602897.62A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2016/0289762 A1 KOH et al. (43) Pub. Date: Oct. 6, 2016 (54) METHODS FOR PROFILIING AND Publication Classification QUANTITATING CELL-FREE RNA (51) Int. Cl. (71) Applicant: The Board of Trustees of the Leland CI2O I/68 (2006.01) Stanford Junior University, Palo Alto, (52) U.S. Cl. CA (US) CPC ....... CI2O 1/6883 (2013.01); C12O 2600/112 (2013.01); C12O 2600/118 (2013.01); C12O (72) Inventors: Lian Chye Winston KOH, Stanford, 2600/158 (2013.01) CA (US); Stephen R. QUAKE, Stanford, CA (US); Hei-Mun Christina FAN, Fremont, CA (US); Wenying (57) ABSTRACT PAN, Stanford, CA (US) The invention generally relates to methods for assessing a (21) Appl. No.: 15/034,746 neurological disorder by characterizing circulating nucleic acids in a blood sample. According to certain embodiments, (22) PCT Filed: Nov. 6, 2014 methods for S. a Nial disorder include (86). PCT No.: PCT/US2O14/064355 obtaining RNA present in a blood sample of a patient Suspected of having a neurological disorder, determining a S 371 (c)(1), level of RNA present in the sample that is specific to brain (2) Date: May 5, 2016 tissue, comparing the sample level of RNA to a reference O O level of RNA specific to brain tissue, determining whether a Related U.S. Application Data difference exists between the sample level and the reference (60) Provisional application No. 61/900,927, filed on Nov. level, and indicating a neurological disorder if a difference 6, 2013. -
The Protein Arginine Methyltransferase PRMT5 Regulates Proliferation
The Protein Arginine Methyltransferase PRMT5 Regulates Proliferation and the Expression of MITF and p27Kip1 in Human Melanoma DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University by Courtney Nicholas Graduate Program in Molecular, Cellular, and Developmental Biology The Ohio State University 2012 Dissertation Committee: Gregory B. Lesinski, PhD, Advisor Jiayuh Lin, PhD Amanda E. Toland, PhD Susheela Tridandapani, PhD Copyright by Courtney Nicholas 2012 Abstract The protein arginine methyltransferase-5 (PRMT5) enzyme is a Type II arginine methyltransferase that can regulate a variety of cellular functions. We hypothesized that PRMT5 plays a unique role in regulating the growth of human melanoma cells. Immunohistochemical analysis indicated significant upregulation of PRMT5 in human melanocytic nevi (88% of specimens positive for PRMT5), malignant melanomas (90% positive) and metastatic melanomas (88% positive) as compared to normal epidermis (5% of specimens positive for PRMT5; p<0.001, Fisher’s exact test). Furthermore, nuclear PRMT5 was significantly decreased in metastatic melanomas as compared to primary cutaneous melanomas (p<0.001, Wilcoxon rank sum test). Human metastatic melanoma cell lines in culture expressed PRMT5 predominantly in the cytoplasm. PRMT5 was found to be associated with its enzymatic cofactor Mep50, but not associated with STAT3 or cyclin D1. However, histologic examination of tumor xenografts from athymic mice revealed a heterogeneous pattern of nuclear and cytoplasmic PRMT5 expression. siRNA-mediated depletion of PRMT5 inhibited proliferation in a subset of melanoma cell lines, while it accelerated the growth of others. Loss of PRMT5 also led to reduced expression of MITF (microphthalmia-associated transcription factor), a melanocyte-lineage specific oncogene, and increased expression of the cell cycle regulator p27Kip1. -
The MER41 Family of Hervs Is Uniquely Involved in the Immune-Mediated Regulation of Cognition/Behavior-Related Genes
bioRxiv preprint doi: https://doi.org/10.1101/434209; this version posted October 3, 2018. 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. The MER41 family of HERVs is uniquely involved in the immune-mediated regulation of cognition/behavior-related genes: pathophysiological implications for autism spectrum disorders Serge Nataf*1, 2, 3, Juan Uriagereka4 and Antonio Benitez-Burraco 5 1CarMeN Laboratory, INSERM U1060, INRA U1397, INSA de Lyon, Lyon-Sud Faculty of Medicine, University of Lyon, Pierre-Bénite, France. 2 University of Lyon 1, Lyon, France. 3Banque de Tissus et de Cellules des Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon, France. 4Department of Linguistics and School of Languages, Literatures & Cultures, University of Maryland, College Park, USA. 5Department of Spanish, Linguistics, and Theory of Literature (Linguistics). Faculty of Philology. University of Seville, Seville, Spain * Corresponding author: [email protected] bioRxiv preprint doi: https://doi.org/10.1101/434209; this version posted October 3, 2018. 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 Interferon-gamma (IFNa prototypical T lymphocyte-derived pro-inflammatory cytokine, was recently shown to shape social behavior and neuronal connectivity in rodents. STAT1 (Signal Transducer And Activator Of Transcription 1) is a transcription factor (TF) crucially involved in the IFN pathway. -
Somatic Mutation Analysis of P53 and ST7 Tumor Suppressor Genes in Gastric Carcinoma by DHPLC
P.O.Box 2345, Beijing 100023,China World J Gastroenterol 2003;9(12):2662-2665 Fax: +86-10-85381893 http://www.paper.edu.cn World Journal of Gastroenterology E-mail: [email protected] www.wjgnet.com Copyright © 2003 by The WJG Press ISSN 1007-9327 • GASTRIC CANCER • Somatic mutation analysis of p53 and ST7 tumor suppressor genes in gastric carcinoma by DHPLC Chong Lu, Hui-Mian Xu, Qun Ren, Yang Ao, Zhen-Ning Wang, Xue Ao, Li Jiang, Yang Luo, Xue Zhang Chong Lu, Hui-Mian Xu, Zhen-Ning Wang, Laboratory of cells in gastric tumor specimens is enough to form Medical Genomics, Oncology Department, the First Affiliated heteroduplex with mutant alleles for DHPLC detection. ST7 Clinical College, China Medical University, Shenyang, 110001, gene may not be the target gene of inactivation at 7q31 site Liaoning Province, China in gastric carcinoma. Qun Ren, Yang Ao, Xue Ao, Li Jiang, Yang Luo, Laboratory of Medical Genomics, China Medical University, Shenyang, 110001, Lu C, Xu HM, Ren Q, Ao Y, Wang ZN, Ao X, Jiang L, Luo Y, Liaoning Province, China Zhang X. Somatic mutation analysis of p53 and ST7 tumor Xue Zhang, Laboratory of Medical Genomics, China Medical suppressor genes in gastric carcinoma by DHPLC. World J University, Shenyang, 110001, Liaoning Province, China. Laboratory Gastroenterol 2003; 9(12): 2662-2665 of Genetics, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100021, China http://www.wjgnet.com/1007-9327/9/2662.asp Supported by National Science Fund for Distinguished Young Scholars, No. 30125017, and the Major State Basic Research Development Program of China (973 Program), No. -
Bacterial Retrons Function in Anti-Phage Defense
Article Bacterial Retrons Function In Anti-Phage Defense Graphical Abstract Authors Adi Millman, Aude Bernheim, Retrons appear in an operon Retrons generate an RNA-DNA hybrid via reverse transcription with additional “effector” genes Avigail Stokar-Avihail, ..., Azita Leavitt, ncRNA Reverse Transcriptase (RT) msDNA Ribosyltransferase Yaara Oppenheimer-Shaanan, (RNA-DNA hybrid) DNA-binding RT Rotem Sorek RNA Retron function 2 transmembrane 5’ G RT domains 2’-5’ 3’ was unknown 3’ RT Correspondence cDNA RT Cold-shock [email protected] 5’ G 2’ 3’ G G cDNA RT RT ATPase Nuclease In Brief reverse transcription RNase H Retrons are part of a large family of anti- Retrons protect bacteria from phage Inhibition of RecBCD by phages triggers retron Ec48 defense phage defense systems that are widespread in bacteria and confer Bacterial density during phage infection Growth resistance against a broad range of B Effector arrest RT D RT activation with retron C B phages, mediated by abortive infection. Effector no retron Ec48 “guards” the bacterial Effector activation leads RecBCD complex to abortive infection bacterial density Retron Ec48 RT 2TM time RecBCD inhibitor B B D D RT Bacteria without retron Bacteria with retron C C B B Phage proteins inhibit RecBCD Retron Ec48 senses RecBCD inhibition Highlights d Retrons are preferentially located in defense islands d Retrons, together with their effector genes, protect bacteria from phages d Protection from phage is mediated by abortive infection d Retron Ec48 guards RecBCD. Inhibition of RecBCD by phages triggers retron defense Millman et al., 2020, Cell 183, 1–11 December 10, 2020 ª 2020 Elsevier Inc. -
Mutations in the ST7/RAY1/HELG Locus Rarely Occur in Primary Colorectal, Gastric, and Hepatocellular Carcinomas
British Journal of Cancer (2003) 88, 1909 – 1913 & 2003 Cancer Research UK All rights reserved 0007 – 0920/03 $25.00 www.bjcancer.com Mutations in the ST7/RAY1/HELG locus rarely occur in primary colorectal, gastric, and hepatocellular carcinomas 1,5 1,5 ,1 1 1 1 1 1 S Yoshimura , T Yamada , S Ohwada* , T Koyama , K Hamada , K Tago , I Sakamoto , I Takeyoshi , T Ikeya2, F Makita3, Y Iino4 and Y Morishita1 1 2 Second Department of Surgery, Gunma University Faculty of Medicine, 3-39-15, Showa-machi, Maebashi, Gunma 371-8511, Japan; Maebashi Red 3 Cross Hospital, 3-21-36, Asahi-cho, Maebashi, Gunma 371-0014, Japan; National Nishi-Gunma Hospital, 2854, Kanai, Shibukawa, Gunma 377-8511, Japan; 4Department of Emergency and Critical Care Medicine, Gunma University Faculty of Medicine, 3-39-15, Showa-machi, Maebashi, Gunma 371-8511, Japan Human cancers frequently show a loss of heterozygosity on chromosome 7q31, which indicates the existence of broad-range tumour-suppressor gene(s) at this locus. Truncating mutations in the ST7 gene at this locus are seen frequently in primary colon cancer and breast cancer cell lines. Therefore, the ST7 gene represents a novel candidate gene for the tumour suppressor at this locus. However, more recent studies have reported that ST7 mutations are infrequent or absent in primary cancer and cell lines. To ascertain the frequency of mutations of the ST7 gene in cancer cells, we examined mutations in the ST7 coding sequence in 48 colorectal, 48 gastric, and 48 hepatocellular carcinomas using polymerase chain reaction–single-strand conformational polymorphism and direct sequencing. -
Lack of Mutations Within ST7 Gene in Tumour-Derived Cell Lines and Primary Epithelial Tumours
British Journal of Cancer (2002) 87, 208 – 211 ª 2002 Cancer Research UK All rights reserved 0007 – 0920/02 $25.00 www.bjcancer.com Short Communication Lack of mutations within ST7 gene in tumour-derived cell lines and primary epithelial tumours VL Brown1, CM Proby1, DM Barnes2 and DP Kelsell*,1 1Centre for Cutaneous Research, Barts and The London, Queen Mary’s School of Medicine and Dentistry, 2 Newark Street, Whitechapel, London E1 2AT, UK; 2Hedley Atkins/Cancer Research UK Breast Pathology Laboratory, Guy’s Hospital, Thomas Guy House, St. Thomas Street, London SE1 9RT, UK ST7 is a candidate tumour suppressor gene at human chromosome locus 7q31.1. We have performed mutational analysis of ST7 in a wide-range of cell lines and primary epithelial cancers and detected only one missense change in a breast cancer cell line. Other mutations previously found in cell lines and primary tumours were not evident in our analysis. These results imply that another tumour suppressor gene at this locus may be more important than ST7 in carcinogenesis. British Journal of Cancer (2002) 87, 208 – 211. doi:10.1038/sj.bjc.6600418 www.bjcancer.com ª 2002 Cancer Research UK Keywords: ST7 gene; mutation; tumour suppressor gene Many strands of evidence point to an important tumour To explore this further, we have performed mutational analysis suppressor gene (TSG) on human chromosome 7q31. Frequent of ST7 exons 3, 5 and 12 in a variety of cell lines (cancerous and deletions within 7q in cytogenetic analyses and a high rate of non-cancerous) and primary epithelial cancer tissues. -
Bacterial Retrons Encode Tripartite Toxin/Antitoxin Systems
bioRxiv preprint doi: https://doi.org/10.1101/2020.06.22.160168; this version posted June 22, 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 4.0 International license. 1 Bacterial retrons encode tripartite toxin/antitoxin systems 2 3 Jacob Bobonis1,2, André Mateus1, Birgit Pfalz1, Sarela Garcia-Santamarina1, Marco Galardini3, 4 Callie Kobayashi4, Frank Stein5, Mikhail M. Savitski1,5,6, Johanna R. Elfenbein7,8*, Helene 5 Andrews-Polymenis4* and Athanasios Typas1,6* 6 7 * Correspondence: [email protected], [email protected] & [email protected] 8 9 1 European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany 10 2 Collaboration for joint PhD degree between EMBL and Heidelberg University, Faculty of Biosciences 11 3 European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, UK 12 4 Texas A&M University, Department of Microbial Pathogenesis and Immunology, Texas, USA 13 5 European Molecular Biology Laboratory, Proteomics Core Facility, Heidelberg, Germany 14 6 European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, 15 Germany 16 7 University of Wisconsin-Madison, Department of Pathobiological Sciences, Madison, WI, USA 17 8 North Carolina State University, Department of Clinical Sciences, Raleigh, NC, USA 18 19 ABSTRACT 20 Retrons are genetic retroelements, commonly found in bacterial genomes and recently 21 repurposed as genome editing tools. Their encoded reverse transcriptase (RT) produces a 22 multi-copy single-stranded DNA (msDNA). Despite our understanding of their complex 23 biosynthesis, the function of msDNAs and therefore, the physiological role of retrons has 24 remained elusive. -
ST7 Polyclonal Antibody
For Research Use Only ST7 Polyclonal antibody Catalog Number:11945-1-AP 1 Publications www.ptgcn.com Catalog Number: GenBank Accession Number: Recommended Dilutions: Basic Information 11945-1-AP BC030954 WB 1:500-1:2000 Size: GeneID (NCBI): IHC 1:50-1:500 700 μg/ml 7982 Source: Full Name: Rabbit suppression of tumorigenicity 7 Isotype: Calculated MW: IgG 63 kDa Purification Method: Observed MW: Antigen affinity purification 63 kDa Immunogen Catalog Number: AG2547 Applications Tested Applications: Positive Controls: IHC, WB,ELISA WB : HeLa cells; mouse brain tissue, Jurkat cells, PC-3 Cited Applications: cells WB IHC : human liver cancer tissue; human pancreas tissue Species Specificity: human, mouse Cited Species: human Note-IHC: suggested antigen retrieval with TE buffer pH 9.0; (*) Alternatively, antigen retrieval may be performed with citrate buffer pH 6.0 Human ST7 (suppressor of tumorigenicity 7) gene, also called FAM4A1, HELG or RAY1, maps to a region on Background Information chromosome 7 identified as an autism-susceptibility locus. ST7 has been proposed to be a tumor suppressor gene with highest expression in heart, liver and pancreas. The product of this gene is a multi-pass membrane protein belonging to the ST7 family, full-length ST7 cDNA has been cloned and verified in cancer cell lines, recent result suggests that ST7 may mediate tumor suppression through the regulation of the genes involved in maintaining the cellular structure of the cell and involved in oncogenic pathways. Notable Publications Author Pubmed ID Journal Application Fengting Yan 24453002 Cancer Res WB Storage: Storage Store at -20ºC. Stable for one year after shipment.