Spliceosomal Usnrnp Biogenesis, Structure and Function Cindy L Will* and Reinhard Lührmann†
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The Expression of NOD2, NLRP3 and NLRC5 and Renal Injury in Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Wang et al. J Transl Med (2019) 17:197 https://doi.org/10.1186/s12967-019-1949-5 Journal of Translational Medicine RESEARCH Open Access The expression of NOD2, NLRP3 and NLRC5 and renal injury in anti-neutrophil cytoplasmic antibody-associated vasculitis Luo‑Yi Wang1,2,3, Xiao‑Jing Sun1,2,3, Min Chen1,2,3* and Ming‑Hui Zhao1,2,3,4 Abstract Background: Nucleotide‑binding oligomerization domain (NOD)‑like receptors (NLRs) are intracellular sensors of pathogens and molecules from damaged cells to regulate the infammatory response in the innate immune system. Emerging evidences suggested a potential role of NLRs in anti‑neutrophil cytoplasmic antibody (ANCA)‑associated vasculitis (AAV). This study aimed to investigate the expression of nucleotide‑binding oligomerization domain con‑ taining protein 2 (NOD2), NOD‑like receptor family pyrin domain containing 3 (NLRP3) and NOD‑like receptor family CARD domain containing 5 (NLRC5) in kidneys of AAV patients, and further explored their associations with clinical and pathological parameters. Methods: Thirty‑four AAV patients in active stage were recruited. Their renal specimens were processed with immu‑ nohistochemistry to assess the expression of three NLRs, and with double immunofuorescence to detect NLRs on intrinsic and infltrating cells. Analysis of gene expression was also adopted in cultured human podocytes. The associa‑ tions between expression of NLRs and clinicopathological parameters were analyzed. Results: The expression of NOD2, NLRP3 and NLRC5 was signifcantly higher in kidneys from AAV patients than those from normal controls, minimal change disease or class IV lupus nephritis. These NLRs co‑localized with podocytes and infltrating infammatory cells. -
Analysis of Gene Expression Data for Gene Ontology
ANALYSIS OF GENE EXPRESSION DATA FOR GENE ONTOLOGY BASED PROTEIN FUNCTION PREDICTION A Thesis Presented to The Graduate Faculty of The University of Akron In Partial Fulfillment of the Requirements for the Degree Master of Science Robert Daniel Macholan May 2011 ANALYSIS OF GENE EXPRESSION DATA FOR GENE ONTOLOGY BASED PROTEIN FUNCTION PREDICTION Robert Daniel Macholan Thesis Approved: Accepted: _______________________________ _______________________________ Advisor Department Chair Dr. Zhong-Hui Duan Dr. Chien-Chung Chan _______________________________ _______________________________ Committee Member Dean of the College Dr. Chien-Chung Chan Dr. Chand K. Midha _______________________________ _______________________________ Committee Member Dean of the Graduate School Dr. Yingcai Xiao Dr. George R. Newkome _______________________________ Date ii ABSTRACT A tremendous increase in genomic data has encouraged biologists to turn to bioinformatics in order to assist in its interpretation and processing. One of the present challenges that need to be overcome in order to understand this data more completely is the development of a reliable method to accurately predict the function of a protein from its genomic information. This study focuses on developing an effective algorithm for protein function prediction. The algorithm is based on proteins that have similar expression patterns. The similarity of the expression data is determined using a novel measure, the slope matrix. The slope matrix introduces a normalized method for the comparison of expression levels throughout a proteome. The algorithm is tested using real microarray gene expression data. Their functions are characterized using gene ontology annotations. The results of the case study indicate the protein function prediction algorithm developed is comparable to the prediction algorithms that are based on the annotations of homologous proteins. -
Differential Analysis of Gene Expression and Alternative Splicing
i bioRxiv preprint doi: https://doi.org/10.1101/2020.08.23.234237; this version posted August 24, 2020. The copyright holder for this preprint i (which was not certified by peer review)“main” is the author/funder, — 2020/8/23 who has — granted 9:38 — bioRxiv page a1 license — #1 to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. i i EmpiReS: Differential Analysis of Gene Expression and Alternative Splicing Gergely Csaba∗, Evi Berchtold*,y, Armin Hadziahmetovic, Markus Gruber, Constantin Ammar and Ralf Zimmer Department of Informatics, Ludwig-Maximilians-Universitat¨ Munchen,¨ 80333, Munich, Germany ABSTRACT to translation. Different transcripts of the same gene are often expressed at the same time, possibly at different abundance, While absolute quantification is challenging in high- yielding a defined mixture of isoforms. Changes to this throughput measurements, changes of features composition are further referred to as differential alternative between conditions can often be determined with splicing (DAS). Various diseases can be linked to DAS high precision. Therefore, analysis of fold changes events (3). Most hallmarks of cancer like tumor progression is the standard method, but often, a doubly and immune escape (4, 5) can be attributed to changes in differential analysis of changes of changes is the transcript composition (6). DAS plays a prominent role required. Differential alternative splicing is an in various types of muscular dystrophy (MD) (7), splicing example of a doubly differential analysis, i.e. fold intervention by targeted exon removal is a therapeutic option changes between conditions for different isoforms in Duchenne MD (8). -
New Approaches to Functional Process Discovery in HPV 16-Associated Cervical Cancer Cells by Gene Ontology
Cancer Research and Treatment 2003;35(4):304-313 New Approaches to Functional Process Discovery in HPV 16-Associated Cervical Cancer Cells by Gene Ontology Yong-Wan Kim, Ph.D.1, Min-Je Suh, M.S.1, Jin-Sik Bae, M.S.1, Su Mi Bae, M.S.1, Joo Hee Yoon, M.D.2, Soo Young Hur, M.D.2, Jae Hoon Kim, M.D.2, Duck Young Ro, M.D.2, Joon Mo Lee, M.D.2, Sung Eun Namkoong, M.D.2, Chong Kook Kim, Ph.D.3 and Woong Shick Ahn, M.D.2 1Catholic Research Institutes of Medical Science, 2Department of Obstetrics and Gynecology, College of Medicine, The Catholic University of Korea, Seoul; 3College of Pharmacy, Seoul National University, Seoul, Korea Purpose: This study utilized both mRNA differential significant genes of unknown function affected by the display and the Gene Ontology (GO) analysis to char- HPV-16-derived pathway. The GO analysis suggested that acterize the multiple interactions of a number of genes the cervical cancer cells underwent repression of the with gene expression profiles involved in the HPV-16- cancer-specific cell adhesive properties. Also, genes induced cervical carcinogenesis. belonging to DNA metabolism, such as DNA repair and Materials and Methods: mRNA differential displays, replication, were strongly down-regulated, whereas sig- with HPV-16 positive cervical cancer cell line (SiHa), and nificant increases were shown in the protein degradation normal human keratinocyte cell line (HaCaT) as a con- and synthesis. trol, were used. Each human gene has several biological Conclusion: The GO analysis can overcome the com- functions in the Gene Ontology; therefore, several func- plexity of the gene expression profile of the HPV-16- tions of each gene were chosen to establish a powerful associated pathway, identify several cancer-specific cel- cervical carcinogenesis pathway. -
Coupling of Spliceosome Complexity to Intron Diversity
bioRxiv preprint doi: https://doi.org/10.1101/2021.03.19.436190; this version posted March 20, 2021. 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. Coupling of spliceosome complexity to intron diversity Jade Sales-Lee1, Daniela S. Perry1, Bradley A. Bowser2, Jolene K. Diedrich3, Beiduo Rao1, Irene Beusch1, John R. Yates III3, Scott W. Roy4,6, and Hiten D. Madhani1,6,7 1Dept. of Biochemistry and Biophysics University of California – San Francisco San Francisco, CA 94158 2Dept. of Molecular and Cellular Biology University of California - Merced Merced, CA 95343 3Department of Molecular Medicine The Scripps Research Institute, La Jolla, CA 92037 4Dept. of Biology San Francisco State University San Francisco, CA 94132 5Chan-Zuckerberg Biohub San Francisco, CA 94158 6Corresponding authors: [email protected], [email protected] 7Lead Contact 1 bioRxiv preprint doi: https://doi.org/10.1101/2021.03.19.436190; this version posted March 20, 2021. 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. SUMMARY We determined that over 40 spliceosomal proteins are conserved between many fungal species and humans but were lost during the evolution of S. cerevisiae, an intron-poor yeast with unusually rigid splicing signals. We analyzed null mutations in a subset of these factors, most of which had not been investigated previously, in the intron-rich yeast Cryptococcus neoformans. -
Molecular Basis for the Distinct Cellular Functions of the Lsm1-7 and Lsm2-8 Complexes
bioRxiv preprint doi: https://doi.org/10.1101/2020.04.22.055376; this version posted April 23, 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. Molecular basis for the distinct cellular functions of the Lsm1-7 and Lsm2-8 complexes Eric J. Montemayor1,2, Johanna M. Virta1, Samuel M. Hayes1, Yuichiro Nomura1, David A. Brow2, Samuel E. Butcher1 1Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA. 2Department of Biomolecular Chemistry, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. Correspondence should be addressed to E.J.M. ([email protected]) and S.E.B. ([email protected]). Abstract Eukaryotes possess eight highly conserved Lsm (like Sm) proteins that assemble into circular, heteroheptameric complexes, bind RNA, and direct a diverse range of biological processes. Among the many essential functions of Lsm proteins, the cytoplasmic Lsm1-7 complex initiates mRNA decay, while the nuclear Lsm2-8 complex acts as a chaperone for U6 spliceosomal RNA. It has been unclear how these complexes perform their distinct functions while differing by only one out of seven subunits. Here, we elucidate the molecular basis for Lsm-RNA recognition and present four high-resolution structures of Lsm complexes bound to RNAs. The structures of Lsm2-8 bound to RNA identify the unique 2′,3′ cyclic phosphate end of U6 as a prime determinant of specificity. In contrast, the Lsm1-7 complex strongly discriminates against cyclic phosphates and tightly binds to oligouridylate tracts with terminal purines. -
Bppart and Bpmax: RNA-RNA Interaction Partition Function and Structure Prediction for the Base Pair Counting Model
BPPart and BPMax: RNA-RNA Interaction Partition Function and Structure Prediction for the Base Pair Counting Model Ali Ebrahimpour-Boroojeny, Sanjay Rajopadhye, and Hamidreza Chitsaz ∗ Department of Computer Science, Colorado State University Abstract A few elite classes of RNA-RNA interaction (RRI), with complex roles in cellular functions such as miRNA-target and lncRNAs in human health, have already been studied. Accordingly, RRI bioinfor- matics tools tailored for those elite classes have been proposed in the last decade. Interestingly, there are somewhat unnoticed mRNA-mRNA interactions in the literature with potentially drastic biological roles. Hence, there is a need for high-throughput generic RRI bioinformatics tools. We revisit our RRI partition function algorithm, piRNA, which happens to be the most comprehensive and computationally-intensive thermodynamic model for RRI. We propose simpler models that are shown to retain the vast majority of the thermodynamic information that piRNA captures. We simplify the energy model and instead consider only weighted base pair counting to obtain BPPart for Base-pair Partition function and BPMax for Base-pair Maximization which are 225 and 1350 faster ◦ × × than piRNA, with a correlation of 0.855 and 0.836 with piRNA at 37 C on 50,500 experimentally charac- terized RRIs. This correlation increases to 0.920 and 0.904, respectively, at 180◦C. − Finally, we apply our algorithm BPPart to discover two disease-related RNAs, SNORD3D and TRAF3, and hypothesize their potential roles in Parkinson's disease and Cerebral Autosomal Dominant Arteri- opathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL). 1 Introduction Since mid 1990s with the advent of RNA interference discovery, RNA-RNA interaction (RRI) has moved to the spotlight in modern, post-genome biology. -
Nuclear Expression of a Group II Intron Is Consistent with Spliceosomal Intron Ancestry
Downloaded from genesdev.cshlp.org on September 30, 2021 - Published by Cold Spring Harbor Laboratory Press Nuclear expression of a group II intron is consistent with spliceosomal intron ancestry Venkata R. Chalamcharla, M. Joan Curcio, and Marlene Belfort1 Center for Medical Sciences, Wadsworth Center, New York State Department of Health, Albany, New York 12208, USA; and School of Public Health, State University of New York at Albany, Albany, New York 12201, USA Group II introns are self-splicing RNAs found in eubacteria, archaea, and eukaryotic organelles. They are mechanistically similar to the metazoan nuclear spliceosomal introns; therefore, group II introns have been invoked as the progenitors of the eukaryotic pre-mRNA introns. However, the ability of group II introns to function outside of the bacteria-derived organelles is debatable, since they are not found in the nuclear genomes of eukaryotes. Here, we show that the Lactococcus lactis Ll.LtrB group II intron splices accurately and efficiently from different pre-mRNAs in a eukaryote, Saccharomyces cerevisiae. However, a pre-mRNA harboring a group II intron is spliced predominantly in the cytoplasm and is subject to nonsense-mediated mRNA decay (NMD), and the mature mRNA from which the group II intron is spliced is poorly translated. In contrast, a pre-mRNA bearing the Tetrahymena group I intron or the yeast spliceosomal ACT1 intron at the same location is not subject to NMD, and the mature mRNA is translated efficiently. Thus, a group II intron can splice from a nuclear transcript, but RNA instability and translation defects would have favored intron loss or evolution into protein-dependent spliceosomal introns, consistent with the bacterial group II intron ancestry hypothesis. -
Striking the Right Balance in Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Striking the Right Balance in Anti-neutrophil Cytoplasmic Antibody-Associated Vasculitis This symposium took place on 4th June 2021, as part of the European Alliance of Associations for Rheumatology (EULAR) virtual congress Speakers: Benjamin Terrier,¹ Joanna Robson,² Bernhard Hellmich³ 1. University of Paris and Hôpital Cochin, France 2. University of the West of England and Bristol Royal Infirmary, UK 3. University of Tübingen, Germany Disclosure: Terrier has been an advisory board member and/or received consulting fees/ travel expenses from AstraZeneca, Chugai, Grifols, GlaxoSmithKline, Janssen, LFB, Octapharma, Roche, and Vifor Pharma. Robson has received speaker’s fees from Roche and Vifor Pharma; and research support from Vifor Pharma. Hellmich has been an investigator in clinical trials for Ab2Bio, AbbVie, AstraZeneca, Bristol- Myers Squibb, Chemocentrix, GlaxoSmithKline, InflaRx, Kiniksa, Nippon Kayaku, Novartis, Roche, and Sanofi. He has acted as a consultant, advisory board member, and/or lecturer for AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Chugai, GlaxoSmithKline, InflaRx, Novartis, Pfizer, Roche, and Vifor Pharma. He is also a member of the Guideline Committees for European Alliance of Associations for Rheumatology (EULAR) and the German Society of Rheumatology (DGRh). Acknowledgements: Writing assistance was provided by Helen Boreham. Support: The publication of this article was funded by Vifor Pharma. The views and opinions expressed are those of the presenters. Content was reviewed by Vifor Pharma for medical accuracy. Citation: Rheumatol. 2021;8[1]:43-50. Meeting Summary Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) causes irreversible short- and long-term damage to vital organs, particularly the kidneys and lungs. Current standard of care (SOC) for AAV, of which glucocorticoids (GC) are a lynchpin, has a number of important limitations: responses to therapy are variable, some patients fail to achieve and sustain remission, and treatment related adverse events (AE) are common. -
Genetic and Genomic Analysis of Hyperlipidemia, Obesity and Diabetes Using (C57BL/6J × TALLYHO/Jngj) F2 Mice
University of Tennessee, Knoxville TRACE: Tennessee Research and Creative Exchange Nutrition Publications and Other Works Nutrition 12-19-2010 Genetic and genomic analysis of hyperlipidemia, obesity and diabetes using (C57BL/6J × TALLYHO/JngJ) F2 mice Taryn P. Stewart Marshall University Hyoung Y. Kim University of Tennessee - Knoxville, [email protected] Arnold M. Saxton University of Tennessee - Knoxville, [email protected] Jung H. Kim Marshall University Follow this and additional works at: https://trace.tennessee.edu/utk_nutrpubs Part of the Animal Sciences Commons, and the Nutrition Commons Recommended Citation BMC Genomics 2010, 11:713 doi:10.1186/1471-2164-11-713 This Article is brought to you for free and open access by the Nutrition at TRACE: Tennessee Research and Creative Exchange. It has been accepted for inclusion in Nutrition Publications and Other Works by an authorized administrator of TRACE: Tennessee Research and Creative Exchange. For more information, please contact [email protected]. Stewart et al. BMC Genomics 2010, 11:713 http://www.biomedcentral.com/1471-2164/11/713 RESEARCH ARTICLE Open Access Genetic and genomic analysis of hyperlipidemia, obesity and diabetes using (C57BL/6J × TALLYHO/JngJ) F2 mice Taryn P Stewart1, Hyoung Yon Kim2, Arnold M Saxton3, Jung Han Kim1* Abstract Background: Type 2 diabetes (T2D) is the most common form of diabetes in humans and is closely associated with dyslipidemia and obesity that magnifies the mortality and morbidity related to T2D. The genetic contribution to human T2D and related metabolic disorders is evident, and mostly follows polygenic inheritance. The TALLYHO/ JngJ (TH) mice are a polygenic model for T2D characterized by obesity, hyperinsulinemia, impaired glucose uptake and tolerance, hyperlipidemia, and hyperglycemia. -
Lymphocyte Separation Medium (LSM
THE JOURNAL OF IMMUNOLOGY Bionetics does it for you. Lymphocyte Separation Medium (LSM wenient One-Step Centrifugation Method _ayer diluted blood on LSM. 2,entrifuge for 30-40 min., 18-20°C, ~.00 x g. ~,spirate and discard plasma layer -larvest lymphocyte layer. Quality Control Assurance Each lot is tested for: • Lymphocyte separation and recovery. • Lymphocyte viability. • Sterility. • Consistent density (1.077-1.080 at 20°C). Packaging • Packaged in amber, screw-cap bottles. • 5 x 100 ml bottles per carton. Storage. • Stored at room temperature. Reference Boyum, A. (1968): Isolation of mononuclear cells and granulocytes from human blood. Scand J. Clin. Lab. Invest. 21, Suppl. 97. Aspirate I IC[OI I IC~ LJI Catalog number: 8410-01 & discard serum Lymphocyte For Laboratory Use Aspirate layer & use (mononuclear Please write for our current Price List and Catalog. cells and Original platelets) ITi BIONETICS° LSM layer Erythrocytes Laboratory Products and Litton granulocytes 5516 Nicholson Lane, Kensington, Maryland 20795 Telephone: (301) 881-1557 1979 Litton Bionetics, tnc Get the most out of your high quality cytotoxic antibodies with LOW-TOX-M RABBIT COMPLEMENT LOW TOXICITY HIGH ACTIVITY Presentation: CL 3051 5 x 1 ml, lyophilized $30.00 When it comes to COMPLEMENT... come to CEDARLANE Direct orders or inquiries to: UNITED STATES: WORLDWIDE EXCEPT U.S. ,4 C~L CEDARLANE ACCURATE CHEMICAL & LABORATO RI ES SCIENTIFIC CORPORATION LIMITED 5516-8TH LINE, R.R. 2 28 TEC STREET, HICKSVtLLE, N.Y. 11801 HORNBY, ONTARIO, CANADA LOP 1E0 Telephone -
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Copyright © 2005 by the Genetics Society of America DOI: 10.1534/genetics.104.034322 Mutations in the Saccharomyces cerevisiae LSM1 Gene That Affect mRNA Decapping and 3 End Protection Sundaresan Tharun,*,1 Denise Muhlrad,† Ashis Chowdhury* and Roy Parker† *Department of Biochemistry, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799 and †Department of Molecular and Cellular Biology and Howard Hughes Medical Institute, University of Arizona, Tucson, Arizona 85721 Manuscript received August 6, 2004 Accepted for publication January 20, 2005 ABSTRACT The decapping of eukaryotic mRNAs is a key step in their degradation. The heteroheptameric Lsm1p–7p complex is a general activator of decapping and also functions in protecting the 3Ј ends of deadenylated mRNAs from a 3Ј-trimming reaction. Lsm1p is the unique member of the Lsm1p–7p complex, distinguish- ing that complex from the functionally different Lsm2p–8p complex. To understand the function of Lsm1p, we constructed a series of deletion and point mutations of the LSM1 gene and examined their effects on phenotype. These studies revealed the following: (i) Mutations affecting the predicted RNA- binding and inter-subunit interaction residues of Lsm1p led to impairment of mRNA decay, suggesting that the integrity of the Lsm1p–7p complex and the ability of the Lsm1p–7p complex to interact with mRNA are important for mRNA decay function; (ii) mutations affecting the predicted RNA contact residues did not affect the localization of the Lsm1p–7p complex to the P-bodies; (iii) mRNA 3Ј-end protection could be indicative of the binding of the Lsm1p–7p complex to the mRNA prior to activation of decapping, since all the mutants defective in mRNA 3Ј end protection were also blocked in mRNA decay; and (iv) in addition to the Sm domain, the C-terminal domain of Lsm1p is also important for mRNA decay function.