The RNA Base-Pairing Problem and Base- Pairing Solutions
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SPEN Induces Mir-4652-3P to Target HIPK2 in Nasopharyngeal Carcinoma
Li et al. Cell Death and Disease (2020) 11:509 https://doi.org/10.1038/s41419-020-2699-2 Cell Death & Disease ARTICLE Open Access SPEN induces miR-4652-3p to target HIPK2 in nasopharyngeal carcinoma Yang Li1,YuminLv1, Chao Cheng2,YanHuang3,LiuYang1, Jingjing He1,XingyuTao1, Yingying Hu1,YutingMa1, Yun Su1,LiyangWu1,GuifangYu4, Qingping Jiang5,ShuLiu6,XiongLiu7 and Zhen Liu1 Abstract SPEN family transcriptional repressor (SPEN), also known as the SMART/HDAC1-associated repressor protein (SHARP), has been reported to modulate the malignant phenotypes of breast cancer, colon cancer, and ovarian cancer. However, its role and the detail molecular basis in nasopharyngeal carcinoma (NPC) remain elusive. In this study, the SPEN mRNA and protein expression was found to be increased in NPC cells and tissues compared with nonmalignant nasopharyngeal epithelial cells and tissues. Elevated SPEN protein expression was found to promote the pathogenesis of NPC and lead to poor prognosis. Knockdown of SPEN expression resulted in inactivation ofPI3K/AKT and c-JUN signaling, thereby suppressing NPC migration and invasion. In addition, miR-4652-3p was found to be a downstream inducer of SPEN by targeting the homeodomain interacting protein kinase 2 (HIPK2) gene, a potential tumor suppressor that reduces the activation of epithelial–mesenchymal transition (EMT) signaling, thereby reducing its expression and leading to increased NPC migration, invasion, and metastasis. In addition, SPEN was found to induce miR-4652-3p expression by activating PI3K/AKT/c-JUN signaling to target HIPK2. Our data provided a new molecular mechanism for SPEN as a metastasis promoter through activation of PI3K/AKT signaling, thereby stimulating the c-JUN/miR-4652-3p axis to target HIPK2 in NPC. -
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. -
Osrrm, a Spen-Like Rice Gene Expressed Specifically in the Endosperm
Shi-Yan Chen et al. npg Cell Research (2007) 17:713-721. npg713 © 2007 IBCB, SIBS, CAS All rights reserved 1001-0602/07 $ 30.00 ORIGINAL ARTICLE www.nature.com/cr OsRRM, a Spen-like rice gene expressed specifically in the endosperm Shi-Yan Chen1, 2, Zong-Yang Wang1, Xiu-Ling Cai1 1National Key Laboratory of Plant Molecular Genetics, Shanghai Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 300 Fenglin Road, Shanghai 200032, China; 2Graduate School of the Chinese Academy of Sciences, 19 Yuquan Road, Beijing 100039, China We used the promoter trap technique to identify a rice plant, named 107#, in which the β-glucuronidase (GUS) reporter gene was expressed specifically in the endosperm. A single copy of the T-DNA was inserted into the plant genome, and a candidate gene OsRRM was identified by the insertion. The OsRRM promoter directed GUS expression specifically in rice endosperm, analogous to the GUS expression pattern observed in 107#. OsRRM is a single-copy gene in rice and encodes a nuclear protein containing 1 005 amino-acid residues with two RNA recognition motifs and one Spen paralog and ortholog C-terminal domain. Western blot analysis confirmed that the OsRRM protein was specifically expressed in rice endosperm. Ectopic expression of OsRRM in transgenic plants led to abnormalities, such as short stature, retarded growth and low fructification rates. Our data, in conjunction with the reported function ofSpen genes, implicated OsRRM in the regulation of cell development in rice endosperm. Keywords: RRM, Spen, promoter trap, GUS, rice Cell Research (2007) 17:713-721. -
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. -
Blood-Based Molecular Biomarker Signatures in Alzheimer's
bioRxiv preprint doi: https://doi.org/10.1101/481879; this version posted December 31, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Article Blood-based molecular biomarker signatures in Alzheimer’s disease: insights from systems biomedicine perspective Tania Islam 1,#, Md. Rezanur Rahman 2,#,*, Md. Shahjaman3, Toyfiquz Zaman2, Md. Rezaul Karim2, Julian M.W. Quinn4, R.M. Damian Holsinger5,6, and Mohammad Ali Moni 6,* 1Department of Biotechnology and Genetic Engineering, Islamic University, Kushtia, Bangladesh; [email protected](T.I.). 2 Department of Biochemistry and Biotechnology, School of Biomedical Science, Khwaja Yunus Ali University, Sirajgonj, Bangladesh; [email protected](M.R.R.). 3 Department of Statistics, Begum Rokeya University, Rangpur, Bangladesh; [email protected] (M.S.). 4 Bone Biology Division, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia;[email protected](J.W.W.Q.). 5 Laboratory of Molecular Neuroscience and Dementia, Brain and Mind Centre, The University of Sydney, Camperdown, NSW, Australia; [email protected] (R.M.D.H.). 6 Discipline of Biomedical Science, School of Medical Sciences, The University of Sydney, Sydney, NSW, Australia; [email protected] (M.A.M.). #These two authors have made an equal contribution and hold joint first authorship for this work. * Correspondence: [email protected] (M.R.R.) or [email protected] (M.A.M.). Abstract: Background and objectives: Alzheimer’s disease (AD) is the progressive neurodegenerative disease characterized by dementia, but no peripheral biomarkers available yet that can detect the AD. -
The Estrogen Receptor Cofactor SPEN Functions As a Tumor Suppressor and Candidate Biomarker of Drug Responsiveness in Hormone-Dependent Breast Cancers
Author Manuscript Published OnlineFirst on August 21, 2015; DOI: 10.1158/0008-5472.CAN-14-3475 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. SPEN is a tumor suppressor in ERα positive breast cancers Title The estrogen receptor cofactor SPEN functions as a tumor suppressor and candidate biomarker of drug responsiveness in hormone-dependent breast cancers. Running Title SPEN is a tumor suppressor in ERα positive breast cancers Authors and affiliations: Légaré, Stéphanie1,2, Cavallone, Luca2, Mamo, Aline2, Chabot, Catherine2, Sirois, Isabelle1,2, Magliocco, Anthony3, Klimowicz, Alexander3, Tonin, Patricia N.4, Buchanan, Marguerite2, Keilty, Dana1,2, Hassan, Saima1,2, Laperrière, David5, Mader, Sylvie5,6, Aleynikova, Olga2, Basik Mark1,2 Keywords - Transcriptional corepressor - Tumor suppressor gene - Estrogen receptor positive breast cancers - Endocrine resistance Financial support • Stéphanie Légaré • Supported by a McGill Integrated Cancer Research Training Program studentship (FRN53888) and a doctoral award from the Fonds de recherche du Québec – Santé. • Isabelle Sirois • Recipient of the Eileen Iwanicki postdoctoral fellowship in Breast Cancer Research from the Canadian Institutes of Health Research in partnership with the Breast Cancer Society of Canada. 1 Dept of Surgery and Oncology, McGill University, Montréal, Québec, Canada. 2 Dept of Oncology and Surgery, Lady Davis Institute for Medical Research, Montréal, Québec, Canada. 3 Dept of Pathology, University of Calgary, Calgary, Alberta, Canada. 4 Depts of Human Genetics and Medicine, McGill University and The Research Institute of the McGill University Health Centre, Montréal, Québec, Canada. 5 Institut de recherche en immunologie et cancérologie, IRIC, Montréal, Québec, Canada. 6 Dept de Biochimie, Université de Montréal, Montréal, Québec, Canada. -
Snipa Snpcard
SNiPAcard Block annotations Block info genomic range chr6:29,970,960-30,792,117 block size 821,158 bp variant count 107 variants Basic features Conservation/deleteriousness Linked genes μ = -0.141 [-3.802 – ABCF1 , AL662797.1 , AL662800.2 , ATAT1 , C6orf136 , DHX16 , FLOT1 4.141] , GNL1 , HCG17 , HCG18 , HCG19P , HCG20 , HCG4P3 , HLA-J , HLA-L , HLA-N , IER3 , LINC00243 , MDC1 , MICC , MRPS18B , NRM , PAIP1P1 , PPP1R10 , PPP1R11 , PPP1R18 , PTMAP1 , RN7SL353P , phyloP gene(s) hit or close-by RNF39 , RPP21 , SUCLA2P1 , TRIM10 , TRIM15 , TRIM26 , TRIM26BP , TRIM31 , TRIM31-AS1 , TRIM39 , TRIM39-RPP21 , TRIM40 , TUBB , UBQLN1P1 , XXbac-BPG252P9.10 , XXbac-BPG252P9.9 , XXbac-BPG283O16.9 , Y_RNA , ZNRD1 , ZNRD1-AS1 , ZNRD1-AS1_3 μ = 0.130 [0 – 1] BTN3A2 , BTN3A3 , C2 , CCHCR1 , CFB , FLOT1 , GABBR1 , HCG17 , HCG20 , HCG22 , HCP5 , HIST1H3I , HLA-A , HLA-B , HLA-C , HLA-F- AS1 , HLA-G , HLA-H , HLA-J , HLA-K , HLA-L , HLA-U , HLA-V , IER3 phastCons eQTL gene(s) , LINC00243 , MICB , NDUFS1 , OR5V1 , PPP1R18 , PSORS1C1 , RNF39 , RPP21 , TMEM154 , TRIM26BP , TRIM31 , TRIM39-RPP21 , VARS2 , WASF5P , ZFP57 , ZNRD1 , ZNRD1-AS1_3 μ = -0.462 [-9.98 – 5.1] ATAT1 , ATAT1 , ATAT1 , ATAT1 , ATAT1 , ATAT1 , ATAT1 , DDR1 , DDR1 , DDR1 , DDR1 , DDR1 , DDR1 , DDR1 , FLOT1 , FLOT1 , FLOT1 , FLOT1 , FLOT1 , FLOT1 , FLOT1 , FLOT1 , HCG19P , HCG19P potentially regulated , HCG19P , HCG19P , HCG19P , HCG19P , HCG19P , NRM , NRM , GERP++ gene(s) NRM , NRM , NRM , NRM , NRM , RNF39 , RNF39 , RNF39 , RNF39 , RNF39 , RNF39 , RNF39 , RNF39 , TRIM26 , TRIM26 , TRIM26 -
SPEN Protein Expression and Interactions with Chromatin in Mouse Testicular Cells
156 3 REPRODUCTIONRESEARCH SPEN protein expression and interactions with chromatin in mouse testicular cells Joanna Korfanty1, Tomasz Stokowy2, Marek Chadalski1, Agnieszka Toma-Jonik1, Natalia Vydra1, Piotr Widłak1, Bartosz Wojtaś3, Bartłomiej Gielniewski3 and Wieslawa Widlak1 1Maria Sklodowska-Curie Institute – Oncology Center, Gliwice Branch, Gliwice, Poland, 2Department of Clinical Science, University of Bergen, Bergen, Norway and 3Laboratory of Molecular Neurobiology, Neurobiology Center, Nencki Institute of Experimental Biology, PAS, Warsaw, Poland Correspondence should be addressed to W Widlak; Email: [email protected] Abstract SPEN (spen family transcription repressor) is a nucleic acid-binding protein putatively involved in repression of gene expression. We hypothesized that SPEN could be involved in general downregulation of the transcription during the heat shock response in mouse spermatogenic cells through its interactions with chromatin. We documented predominant nuclear localization of the SPEN protein in spermatocytes and round spermatids, which was retained after heat shock. Moreover, the protein was excluded from the highly condensed chromatin. Chromatin immunoprecipitation experiments clearly indicated interactions of SPEN with chromatin in vivo. However, ChIP-Seq analyses did not reveal any strong specific peaks both in untreated and heat shocked cells, which might suggest dispersed localization of SPEN and/or its indirect binding to DNA. Using in situ proximity ligation assay we found close in vivo associations of SPEN with MTA1 (metastasis-associated 1), a member of the nucleosome remodeling complex with histone deacetylase activity, which might contribute to interactions of SPEN with chromatin. Reproduction (2018) 156 195–206 Introduction However, regulation of osteocalcin expression by SPEN depends on its interactions with other proteins. -
Whole Exome Sequencing Reveals NOTCH1 Mutations in Anaplastic Large Cell Lymphoma and Points to Notch Both As a Key Pathway and a Potential Therapeutic Target
Non-Hodgkin Lymphoma SUPPLEMENTARY APPENDIX Whole exome sequencing reveals NOTCH1 mutations in anaplastic large cell lymphoma and points to Notch both as a key pathway and a potential therapeutic target Hugo Larose, 1,2 Nina Prokoph, 1,2 Jamie D. Matthews, 1 Michaela Schlederer, 3 Sandra Högler, 4 Ali F. Alsulami, 5 Stephen P. Ducray, 1,2 Edem Nuglozeh, 6 Mohammad Feroze Fazaludeen, 7 Ahmed Elmouna, 6 Monica Ceccon, 2,8 Luca Mologni, 2,8 Carlo Gambacorti-Passerini, 2,8 Gerald Hoefler, 9 Cosimo Lobello, 2,10 Sarka Pospisilova, 2,10,11 Andrea Janikova, 2,11 Wilhelm Woessmann, 2,12 Christine Damm-Welk, 2,12 Martin Zimmermann, 13 Alina Fedorova, 14 Andrea Malone, 15 Owen Smith, 15 Mariusz Wasik, 2,16 Giorgio Inghirami, 17 Laurence Lamant, 18 Tom L. Blundell, 5 Wolfram Klapper, 19 Olaf Merkel, 2,3 G. A. Amos Burke, 20 Shahid Mian, 6 Ibraheem Ashankyty, 21 Lukas Kenner 2,3,22 and Suzanne D. Turner 1,2,10 1Department of Pathology, University of Cambridge, Cambridge, UK; 2European Research Initiative for ALK Related Malignancies (ERIA; www.ERIALCL.net ); 3Department of Pathology, Medical University of Vienna, Vienna, Austria; 4Unit of Laboratory Animal Pathology, Uni - versity of Veterinary Medicine Vienna, Vienna, Austria; 5Department of Biochemistry, University of Cambridge, Tennis Court Road, Cam - bridge, UK; 6Molecular Diagnostics and Personalised Therapeutics Unit, Colleges of Medicine and Applied Medical Sciences, University of Ha’il, Ha’il, Saudi Arabia; 7Neuroinflammation Research Group, Department of Neurobiology, A.I Virtanen Institute -
Effect of Cigarette Smoke on DNA Methylation and Lung Function
de Vries et al. Respiratory Research (2018) 19:212 https://doi.org/10.1186/s12931-018-0904-y RESEARCH Open Access From blood to lung tissue: effect of cigarette smoke on DNA methylation and lung function Maaike de Vries1,2* , Diana A van der Plaat1,2, Ivana Nedeljkovic3, Rikst Nynke Verkaik-Schakel4, Wierd Kooistra2,5, Najaf Amin3, Cornelia M van Duijn3, Corry-Anke Brandsma2,5, Cleo C van Diemen6, Judith M Vonk1,2 and H Marike Boezen1,2 Abstract Background: Genetic and environmental factors play a role in the development of COPD. The epigenome, and more specifically DNA methylation, is recognized as important link between these factors. We postulate that DNA methylation is one of the routes by which cigarette smoke influences the development of COPD. In this study, we aim to identify CpG-sites that are associated with cigarette smoke exposure and lung function levels in whole blood and validate these CpG-sites in lung tissue. Methods: The association between pack years and DNA methylation was studied genome-wide in 658 current smokers with >5 pack years using robust linear regression analysis. Using mediation analysis, we subsequently selected the CpG-sites that were also associated with lung function levels. Significant CpG-sites were validated in lung tissue with pyrosequencing and expression quantitative trait methylation (eQTM) analysis was performed to investigate the association between DNA methylation and gene expression. Results: 15 CpG-sites were significantly associated with pack years and 10 of these were additionally associated with lung function levels. We validated 5 CpG-sites in lung tissue and found several associations between DNA methylation and gene expression. -
A Conserved Structural Motif Reveals the Essential Transcriptional Repression Function of Spen Proteins and Their Role in Developmental Signaling
Downloaded from genesdev.cshlp.org on September 29, 2021 - Published by Cold Spring Harbor Laboratory Press A conserved structural motif reveals the essential transcriptional repression function of Spen proteins and their role in developmental signaling Mariko Ariyoshi and John W.R. Schwabe1 Medical Research Council, Laboratory of Molecular Biology, Cambridge CB2 2QH, UK Spen proteins regulate the expression of key transcriptional effectors in diverse signaling pathways. They are large proteins characterized by N-terminal RNA-binding motifs and a highly conserved C-terminal SPOC domain. The specific biological role of the SPOC domain (Spen paralog and ortholog C-terminal domain), and hence, the common function of Spen proteins, has been unclear to date. The Spen protein, SHARP (SMRT/HDAC1-associated repressor protein), was identified as a component of transcriptional repression complexes in both nuclear receptor and Notch/RBP-J signaling pathways. We have determined the 1.8 Å crystal structure of the SPOC domain from SHARP. This structure shows that essentially all of the conserved surface residues map to a positively charged patch. Structure-based mutational analysis indicates that this conserved region is responsible for the interaction between SHARP and the universal transcriptional corepressor SMRT/NCoR (silencing mediator for retinoid and thyroid receptors/nuclear receptor corepressor. We demonstrate that this interaction involves a highly conserved acidic motif at the C terminus of SMRT/NCoR. These findings suggest that the conserved function of the SPOC domain is to mediate interaction with SMRT/NCoR corepressors, and that Spen proteins play an essential role in the repression complex. [Keywords: SHARP; SPOC domain; Spen proteins; transcriptional corepressor; crystal structure; nuclear receptor] Received March 31, 2003; revised version accepted June 3, 2003. -
Tubulin Gene (TUBB) in the HLA Class I Region May Provide the Genetic Basis for HLA-Linked Microtubule Dysfunction
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Universität München: Elektronischen Publikationen Hum Genet (1994) 93:42-46 human .. genetics Springer-Verlag 1994 Presence of an expressed 13-tubulin gene (TUBB) in the HLA class I region may provide the genetic basis for HLA-linked microtubule dysfunction Armin Volz 1, Elisabeth Weiss 2, John Trowsdale 3, Andreas Ziegler 1 Institut ftir Experimentelle Onkologie und Transplantationsmedizin, Universit~itsklinikum Rudolf Virchow, Freie Universit~it Berlin, Berlin, Germany 2 Institut ftir Anthropologie und Humangenetik, Universit~it Mtinchen, M0nchen, Germany 3 Human ]mmunogenetics Laboratory, ICRF Laboratories, London, UK Received: 21 April 1993 / Revised: 7 June 1993 Abstract. An expressed I]-tubulin gene (TUBB) has pre- of cell shape during interphase. They consist of ffJ[3 tubu- viously been localized to chromosome region 6pter-p21 lin heterodimers, which are closely related polypeptides. in man. By using a panel of deletion mutant cell lines and Four classes of [3-tubulins, characterized by their amino radiation-reduced hybrids containing fragments of chro- acid sequence, have been described; the class I isotype mosome 6, the TUBB locus could be mapped to the HLA is the major constitutively expressed 13-tubulin (Lopata class I region at 6p21.3. A long range restriction map in- and Cleveland 1987). The human ~3-tubulin class 1 gene, cluding TUBB and several HLA class I genes was then TUBB (originally named M40 or hi31), has previously generated by rotating field gel electrophoresis. The results been mapped to chromosome region 6pter-p21 (Floyd- show that TUBB maps to a segment 170-370 kb telomeric Smith et al.