Insights Into the Structure and Function of Est3 from the Hansenula Polymorpha Telomerase Nikita M
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Human Nonsense-Mediated RNA Decay Initiates Widely by Endonucleolysis and Targets Snorna Host Genes
Downloaded from genesdev.cshlp.org on October 2, 2021 - Published by Cold Spring Harbor Laboratory Press Human nonsense-mediated RNA decay initiates widely by endonucleolysis and targets snoRNA host genes Søren Lykke-Andersen,1,4 Yun Chen,2,4 Britt R. Ardal,1 Berit Lilje,2 Johannes Waage,2,3 Albin Sandelin,2 and Torben Heick Jensen1 1Centre for mRNP Biogenesis and Metabolism, Department of Molecular Biology and Genetics, Aarhus University, Aarhus DK-8000, Denmark; 2The Bioinformatics Centre, Department of Biology and Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen DK-2200, Denmark Eukaryotic RNAs with premature termination codons (PTCs) are eliminated by nonsense-mediated decay (NMD). While human nonsense RNA degradation can be initiated either by an endonucleolytic cleavage event near the PTC or through decapping, the individual contribution of these activities on endogenous substrates has remained unresolved. Here we used concurrent transcriptome-wide identification of NMD substrates and their 59–39 decay intermediates to establish that SMG6-catalyzed endonucleolysis widely initiates the degradation of human nonsense RNAs, whereas decapping is used to a lesser extent. We also show that a large proportion of genes hosting snoRNAs in their introns produce considerable amounts of NMD-sensitive splice variants, indicating that these RNAs are merely by-products of a primary snoRNA production process. Additionally, transcripts from genes encoding multiple snoRNAs often yield alternative transcript isoforms that allow for differential expression of individual coencoded snoRNAs. Based on our findings, we hypothesize that snoRNA host genes need to be highly transcribed to accommodate high levels of snoRNA production and that the expression of individual snoRNAs and their cognate spliced RNA can be uncoupled via alternative splicing and NMD. -
A Genome-Wide Association Study of a Coronary Artery Disease Risk Variant
Journal of Human Genetics (2013) 58, 120–126 & 2013 The Japan Society of Human Genetics All rights reserved 1434-5161/13 www.nature.com/jhg ORIGINAL ARTICLE A genome-wide association study of a coronary artery diseaseriskvariant Ji-Young Lee1,16, Bok-Soo Lee2,16, Dong-Jik Shin3,16, Kyung Woo Park4,16, Young-Ah Shin1, Kwang Joong Kim1, Lyong Heo1, Ji Young Lee1, Yun Kyoung Kim1, Young Jin Kim1, Chang Bum Hong1, Sang-Hak Lee3, Dankyu Yoon5, Hyo Jung Ku2, Il-Young Oh4, Bong-Jo Kim1, Juyoung Lee1, Seon-Joo Park1, Jimin Kim1, Hye-kyung Kawk1, Jong-Eun Lee6, Hye-kyung Park1, Jae-Eun Lee1, Hye-young Nam1, Hyun-young Park7, Chol Shin8, Mitsuhiro Yokota9, Hiroyuki Asano10, Masahiro Nakatochi11, Tatsuaki Matsubara12, Hidetoshi Kitajima13, Ken Yamamoto13, Hyung-Lae Kim14, Bok-Ghee Han1, Myeong-Chan Cho15, Yangsoo Jang3,17, Hyo-Soo Kim4,17, Jeong Euy Park2,17 and Jong-Young Lee1,17 Although over 30 common genetic susceptibility loci have been identified to be independently associated with coronary artery disease (CAD) risk through genome-wide association studies (GWAS), genetic risk variants reported to date explain only a small fraction of heritability. To identify novel susceptibility variants for CAD and confirm those previously identified in European population, GWAS and a replication study were performed in the Koreans and Japanese. In the discovery stage, we genotyped 2123 cases and 3591 controls with 521 786 SNPs using the Affymetrix SNP Array 6.0 chips in Korean. In the replication, direct genotyping was performed using 3052 cases and 4976 controls from the KItaNagoya Genome study of Japan with 14 selected SNPs. -
Supplementary Table 3 Complete List of RNA-Sequencing Analysis of Gene Expression Changed by ≥ Tenfold Between Xenograft and Cells Cultured in 10%O2
Supplementary Table 3 Complete list of RNA-Sequencing analysis of gene expression changed by ≥ tenfold between xenograft and cells cultured in 10%O2 Expr Log2 Ratio Symbol Entrez Gene Name (culture/xenograft) -7.182 PGM5 phosphoglucomutase 5 -6.883 GPBAR1 G protein-coupled bile acid receptor 1 -6.683 CPVL carboxypeptidase, vitellogenic like -6.398 MTMR9LP myotubularin related protein 9-like, pseudogene -6.131 SCN7A sodium voltage-gated channel alpha subunit 7 -6.115 POPDC2 popeye domain containing 2 -6.014 LGI1 leucine rich glioma inactivated 1 -5.86 SCN1A sodium voltage-gated channel alpha subunit 1 -5.713 C6 complement C6 -5.365 ANGPTL1 angiopoietin like 1 -5.327 TNN tenascin N -5.228 DHRS2 dehydrogenase/reductase 2 leucine rich repeat and fibronectin type III domain -5.115 LRFN2 containing 2 -5.076 FOXO6 forkhead box O6 -5.035 ETNPPL ethanolamine-phosphate phospho-lyase -4.993 MYO15A myosin XVA -4.972 IGF1 insulin like growth factor 1 -4.956 DLG2 discs large MAGUK scaffold protein 2 -4.86 SCML4 sex comb on midleg like 4 (Drosophila) Src homology 2 domain containing transforming -4.816 SHD protein D -4.764 PLP1 proteolipid protein 1 -4.764 TSPAN32 tetraspanin 32 -4.713 N4BP3 NEDD4 binding protein 3 -4.705 MYOC myocilin -4.646 CLEC3B C-type lectin domain family 3 member B -4.646 C7 complement C7 -4.62 TGM2 transglutaminase 2 -4.562 COL9A1 collagen type IX alpha 1 chain -4.55 SOSTDC1 sclerostin domain containing 1 -4.55 OGN osteoglycin -4.505 DAPL1 death associated protein like 1 -4.491 C10orf105 chromosome 10 open reading frame 105 -4.491 -
Arabidopsis SMG7 Protein Is Required for Exit from Meiosis
2208 Research Article Arabidopsis SMG7 protein is required for exit from meiosis Nina Riehs1,*, Svetlana Akimcheva1,*, Jasna Puizina1,‡, Petra Bulankova1, Rachel A. Idol2,§, Jiri Siroky3, Alexander Schleiffer4, Dieter Schweizer1, Dorothy E. Shippen2 and Karel Riha1,¶ 1Gregor Mendel Institute of Molecular Plant Biology, Austrian Academy of Sciences, Dr Bohr-Gasse 3, 1030 Vienna, Austria 2Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843-2128, USA 3Institute of Biophysics, Czech Academy of Sciences, 612 65 Brno, Czech Republic 4Research Institute of Molecular Pathology, 1030 Vienna, Austria *These authors contributed equally to this work ‡Present address: Department of Biology, University of Split, Teslina 12, Croatia §Present address: Department of Internal Medicine, Division of Hematology, Division of Laboratory Medicine, Washington University School of Medicine, St Louis, MO 63110, USA ¶Author for correspondence (e-mail: [email protected]) Accepted 9 April 2008 Journal of Cell Science 121, 2208-2216 Published by The Company of Biologists 2008 doi:10.1242/jcs.027862 Summary Meiosis consists of two nuclear divisions that are separated by that is characterized by delayed chromosome decondensation a short interkinesis. Here we show that the SMG7 protein, which and aberrant rearrangement of the meiotic spindle. The smg7 plays an evolutionarily conserved role in nonsense-mediated phenotype was mimicked by exposing meiocytes to the RNA decay (NMD) in animals and yeast, is essential for the proteasome inhibitor MG115. Together, these data indicate that progression from anaphase to telophase in the second meiotic SMG7 counteracts cyclin-dependent kinase (CDK) activity at division in Arabidopsis. Arabidopsis SMG7 is an essential gene, the end of meiosis, and reveal a novel link between SMG7 and the disruption of which causes embryonic lethality. -
Quality Control of Eukaryotic Mrna: Safeguarding Cells from Abnormal Mrna Function
Downloaded from genesdev.cshlp.org on October 2, 2021 - Published by Cold Spring Harbor Laboratory Press REVIEW Quality control of eukaryotic mRNA: safeguarding cells from abnormal mRNA function Olaf Isken and Lynne E. Maquat1 Department of Biochemistry and Biophysics, School of Medicine and Dentistry, University of Rochester, Rochester, New York 14642, USA Cells routinely make mistakes. Some mistakes are en- (Dreyfuss et al. 2002). RNA-associated proteins not only coded by the genome and may manifest as inherited or reflect the history of the RNA but may also influence acquired diseases. Other mistakes occur because meta- future steps of RNA metabolism (Giorgi and Moore bolic processes can be intrinsically inefficient or inaccu- 2007). rate. Consequently, cells have developed mechanisms to Cells have evolved pathways to eliminate RNAs that minimize the damage that would result if mistakes went are incorrectly processed or improperly function either unchecked. Here, we provide an overview of three qual- because of mutations within the genes that encode them ity control mechanisms—nonsense-mediated mRNA de- or because of mistakes made during their metabolism cay, nonstop mRNA decay, and no-go mRNA decay. and/or function in the absence of mutations within their Each surveys mRNAs during translation and degrades genes. This review will focus on pathways that eliminate those mRNAs that direct aberrant protein synthesis. defective mRNAs as a consequence of their inability to Along with other types of quality control that occur dur- properly direct protein synthesis. These pathways en- ing the complex processes of mRNA biogenesis, these compass the translation-dependent mechanisms of mRNA surveillance mechanisms help to ensure the in- cytoplasmic surveillance. -
Aneuploidy: Using Genetic Instability to Preserve a Haploid Genome?
Health Science Campus FINAL APPROVAL OF DISSERTATION Doctor of Philosophy in Biomedical Science (Cancer Biology) Aneuploidy: Using genetic instability to preserve a haploid genome? Submitted by: Ramona Ramdath In partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biomedical Science Examination Committee Signature/Date Major Advisor: David Allison, M.D., Ph.D. Academic James Trempe, Ph.D. Advisory Committee: David Giovanucci, Ph.D. Randall Ruch, Ph.D. Ronald Mellgren, Ph.D. Senior Associate Dean College of Graduate Studies Michael S. Bisesi, Ph.D. Date of Defense: April 10, 2009 Aneuploidy: Using genetic instability to preserve a haploid genome? Ramona Ramdath University of Toledo, Health Science Campus 2009 Dedication I dedicate this dissertation to my grandfather who died of lung cancer two years ago, but who always instilled in us the value and importance of education. And to my mom and sister, both of whom have been pillars of support and stimulating conversations. To my sister, Rehanna, especially- I hope this inspires you to achieve all that you want to in life, academically and otherwise. ii Acknowledgements As we go through these academic journeys, there are so many along the way that make an impact not only on our work, but on our lives as well, and I would like to say a heartfelt thank you to all of those people: My Committee members- Dr. James Trempe, Dr. David Giovanucchi, Dr. Ronald Mellgren and Dr. Randall Ruch for their guidance, suggestions, support and confidence in me. My major advisor- Dr. David Allison, for his constructive criticism and positive reinforcement. -
Genome-Wide Transcriptional Sequencing Identifies Novel Mutations in Metabolic Genes in Human Hepatocellular Carcinoma DAOUD M
CANCER GENOMICS & PROTEOMICS 11 : 1-12 (2014) Genome-wide Transcriptional Sequencing Identifies Novel Mutations in Metabolic Genes in Human Hepatocellular Carcinoma DAOUD M. MEERZAMAN 1,2 , CHUNHUA YAN 1, QING-RONG CHEN 1, MICHAEL N. EDMONSON 1, CARL F. SCHAEFER 1, ROBERT J. CLIFFORD 2, BARBARA K. DUNN 3, LI DONG 2, RICHARD P. FINNEY 1, CONSTANCE M. CULTRARO 2, YING HU1, ZHIHUI YANG 2, CU V. NGUYEN 1, JENNY M. KELLEY 2, SHUANG CAI 2, HONGEN ZHANG 2, JINGHUI ZHANG 1,4 , REBECCA WILSON 2, LAUREN MESSMER 2, YOUNG-HWA CHUNG 5, JEONG A. KIM 5, NEUNG HWA PARK 6, MYUNG-SOO LYU 6, IL HAN SONG 7, GEORGE KOMATSOULIS 1 and KENNETH H. BUETOW 1,2 1Center for Bioinformatics and Information Technology, National Cancer Institute, Rockville, MD, U.S.A.; 2Laboratory of Population Genetics, National Cancer Institute, National Cancer Institute, Bethesda, MD, U.S.A.; 3Basic Prevention Science Research Group, Division of Cancer Prevention, National Cancer Institute, Bethesda, MD, U.S.A; 4Department of Biotechnology/Computational Biology, St. Jude Children’s Research Hospital, Memphis, TN, U.S.A.; 5Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea; 6Department of Internal Medicine, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, Korea; 7Department of Internal Medicine, College of Medicine, Dankook University, Cheon-An, Korea Abstract . We report on next-generation transcriptome Worldwide, liver cancer is the fifth most common cancer and sequencing results of three human hepatocellular carcinoma the third most common cause of cancer-related mortality (1). tumor/tumor-adjacent pairs. -
A Protein with Similarities to Caenorhabditis Elegans SMG5 and SMG7 That Functions in the Dephosphorylation of Upf1
Downloaded from rnajournal.cshlp.org on October 5, 2021 - Published by Cold Spring Harbor Laboratory Press Characterization of human Smg5/7a: A protein with similarities to Caenorhabditis elegans SMG5 and SMG7 that functions in the dephosphorylation of Upf1 SHANG-YI CHIU,1 GUILLAUME SERIN,1,3 OSAMU OHARA,2 and LYNNE E. MAQUAT1 1Department of Biochemistry and Biophysics, School of Medicine and Dentistry, University of Rochester, Rochester, New York 14642, USA 2Department of Human Gene Research, Kazusa DNA Research Institute, Kisarazu, Chiba 292-0812, Japan; Immunogenomics Research Team, RIKEN Research Center for Allergy and Immunology, Yokohama, Japan ABSTRACT Nonsense-mediated mRNA decay (NMD) in mammalian cells depends on phosphorylation of Upf1, an RNA-dependent ATPase and 5-to-3 helicase. Upf1 phosphorylation is mediated by Smg1, a phosphoinositol 3-kinase–related protein kinase. Here, we describe a human protein, which we call hSmg5/7a, that manifests similarity to Caenorhabditis elegans NMD factors CeSMG5 and CeSMG7, as well as two Drosophila melanogaster proteins that are also similar to the C. elegans NMD factors. Results indicate that hSmg5/7a functions in the dephosphorylation of Upf1. Furthermore, hSmg5/7a copurifies with Upf1, Upf2, Upf3X, Smg1, and the catalytic subunit of protein phosphatase 2A. We also demonstrate that Upf2, another factor involved in NMD, is a phosphoprotein. However, hSmg5/7a plays no role in the dephosphorylation of Upf2. These data indicate that hSmg5/7a targets protein phosphatase 2A to Upf1 but not -
TERRA: Telomeric Repeat-Containing RNA
The EMBO Journal (2009) 28, 2503–2510 | & 2009 European Molecular Biology Organization | Some Rights Reserved 0261-4189/09 www.embojournal.org TTHEH E EEMBOMBO JJOURNALOURN AL Focus Review TERRA: telomeric repeat-containing RNA Brian Luke1,2 and Joachim Lingner1,2,* lytic processing of chromosome ends and the end replication problem. This shortening can be counteracted by the cellular 1EPFL-Ecole Polytechnique Fe´de´rale de Lausanne, ISREC-Swiss Institute for Experimental Cancer Research, Lausanne, Switzerland and reverse-transcriptase telomerase, which uses an internal RNA 2‘Frontiers in Genetics’ National Center for Competence in Research moiety as a template for the synthesis of telomere repeats (NCCR), Geneva, Switzerland (Cech, 2004; Blackburn et al, 2006). Telomerase is regulated at individual chromosome ends through telomere-binding Telomeres, the physical ends of eukaryotic chromosomes, proteins to mediate telomere length homoeostasis; however, consist of tandem arrays of short DNA repeats and a large in humans, telomerase is expressed in most tissues only set of specialized proteins. A recent analysis has identified during the first weeks of embryogenesis (Ulaner and telomeric repeat-containing RNA (TERRA), a large non- Giudice, 1997). Repression of telomerase in somatic cells is coding RNA in animals and fungi, which forms an integral thought to result in a powerful tumour-suppressive function. component of telomeric heterochromatin. TERRA tran- Short telomeres that accumulate following an excessive scription occurs at most or all chromosome ends and it number of cell division cycles induce cellular senescence, is regulated by RNA surveillance factors and in response to and this counteracts the growth of pre-malignant lesions. -
Intrinsic Disorder in Tetratricopeptide Repeat Proteins
International Journal of Molecular Sciences Article Intrinsic Disorder in Tetratricopeptide Repeat Proteins 1, 1, 1, 2 Nathan W. Van Bibber y, Cornelia Haerle y, Roy Khalife y, Bin Xue and Vladimir N. Uversky 1,3,4,* 1 Department of Molecular Medicine Morsani College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd., Tampa, FL 33612, USA; [email protected] (N.W.V.B.); [email protected] (C.H.); [email protected] (R.K.) 2 Department of Cell Biology, Microbiology and Molecular Biology, School of Natural Sciences and Mathematics, College of Arts and Sciences, University of South Florida, Tampa, FL 33620, USA; [email protected] 3 USF Health Byrd Alzheimer’s Research Institute, Morsani College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd., Tampa, FL 33612, USA 4 Institute for Biological Instrumentation, Russian Academy of Sciences, Federal Research Center “Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences”, 4 Institutskaya St., Pushchino, 142290 Moscow Region, Russia * Correspondence: [email protected]; Tel.: +1-813-974-5816; Fax: +1-813-974-7357 These authors contributed equally to this work. y Received: 21 April 2020; Accepted: 22 May 2020; Published: 25 May 2020 Abstract: Among the realm of repeat containing proteins that commonly serve as “scaffolds” promoting protein-protein interactions, there is a family of proteins containing between 2 and 20 tetratricopeptide repeats (TPRs), which are functional motifs consisting of 34 amino acids. The most distinguishing feature of TPR domains is their ability to stack continuously one upon the other, with these stacked repeats being able to affect interaction with binding partners either sequentially or in combination. -
Effects of Simulated Microgravity on the Expression Profiles of RNA
Effects of simulated microgravity on the expression profiles of RNA during osteogenic differentiation of human bone marrow mesenchymal stem cells Ping Chen, Emory University L Li, Zhejiang University C Zhang, Zhejiang University F-F Hong, Zhejiang University J-F Wang, Zhejiang University Journal Title: CELL PROLIFERATION Volume: Volume 52, Number 2 Publisher: WILEY | 2019-03-01, Pages e12539-e12539 Type of Work: Article Publisher DOI: 10.1111/cpr.12539 Permanent URL: https://pid.emory.edu/ark:/25593/vk2g5 Final published version: http://dx.doi.org/10.1111/cpr.12539 Accessed September 28, 2021 3:40 PM EDT Received: 5 July 2018 | Revised: 16 August 2018 | Accepted: 4 September 2018 DOI: 10.1111/cpr.12539 ORIGINAL ARTICLE Effects of simulated microgravity on the expression profiles of RNA during osteogenic differentiation of human bone marrow mesenchymal stem cells Liang Li1 | Cui Zhang1 | Jian‐ling Chen1 | Fan‐fan Hong1 | Ping Chen2 | Jin‐fu Wang1 1Institute of Cell and Development Biology, College of Life Sciences, Zhejiang University, Abstract Hangzhou, China Objectives: Exposure to microgravity induces many adaptive and pathological 2 Departments of Cell Biology and changes in human bone marrow mesenchymal stem cells (hBMSCs). However, the Otolaryngology, Emory University School of Medicine, Atlanta, Georgia underlying mechanisms of these changes are poorly understood. We revealed the gene expression patterns of hBMSCs under normal ground (NG) and simulated mi‐ Correspondence Jin‐Fu Wang, Institute of Cell and crogravity (SMG), which -
Common Genetic Variants and Subclinical Atherosclerosis: the Multi-Ethnic Study of Atherosclerosis
Common Genetic Variants and Subclinical Atherosclerosis: The Multi-Ethnic Study of Atherosclerosis (MESA). Authors Authors: Jose D. Vargas, Ani Manichaikul, Xin Q. Wang, Stephen S. Rich, Jerome I. Rotter, Wendy S. Post, Joseph F. Polak, Matthew J. Budoff, and David A. Bluemke. Abstract Background: Subclinical atherosclerosis (sCVD), measured by coronary artery calcium (CAC) and carotid intima media thickness (CIMT) has been associated with cardiovascular disease (CVD). Genome Wide Association Studies (GWAS) of CVD have focused on Caucasian populations. We hypothesized that these associations would differ in populations from distinct genetic backgrounds. Methods and Results: The associations between sCVD and 66 single nucleotide polymorphisms (SNPs) from published GWAS of sCVD and CVD were tested in 8224 Multi-Ethnic Study of Atherosclerosis (MESA) and MESA Family participants (2685 Caucasians (EUA), 777 Chinese (CHN), 2588 African Americans (AFA), and 2174 Hispanic (HIS)) using an additive model adjusting for CVD risk factors, with SNP significance defined by a Bonferroni-corrected p < 7.6 x 10-4 (0.05/66). Results: In EUA there were significant associations with CAC in 9p21 (rs1333049, P=2 x 10-9; rs4977574, P= 4 x 10-9), COL4A1 (rs9515203, P=9 x 10-6), and PHACTR1 (rs9349379, P= 4 x 10-4). In HIS, SNPs were associated with CAC in 9p21 (rs1333049, P=8 x 10-5; rs4977574, P=5 x 10-5), APOA5 (rs964184, P=2 x 10-4), and ADAMTS7 (rs7173743, P=4 x 10-4). There were no associations with the 9p21 region in AFA and CHN. Fine mapping of the 9p21 region revealed SNPs with robust associations with CAC in EUA and HIS but no significant associations in AFA and CHN.