DOCSLIB.ORG

Research Article Low GAS5 Levels As a Predictor of Poor Survival in Patients with Lower-Grade Gliomas

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Research Article Low GAS5 Levels As a Predictor of Poor Survival in Patients with Lower-Grade Gliomas Hindawi Journal of Oncology Volume 2019, Article ID 1785042, 15 pages https://doi.org/10.1155/2019/1785042 Research Article Low GAS5 Levels as a Predictor of Poor Survival in Patients with Lower-Grade Gliomas Yanfang Wang ,1 Shan Xin,1 Kai Zhang,2 Run Shi ,1 and Xuanwen Bao 3,4 1 Ludwig-Maximilians-Universitat¨ Munchen¨ (LMU), 80539 Munich, Germany 2Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 310016 Hangzhou, China 3Institute of Radiation Biology, Helmholtz Center Munich, German Research Center for Environmental Health, 85764 Neuherberg, Germany 4Technical University Munich (TUM), 80333 Munich, Germany Correspondence should be addressed to Run Shi; [email protected] and Xuanwen Bao; [email protected] Received 1 October 2018; Revised 18 December 2018; Accepted 3 January 2019; Published 3 February 2019 Academic Editor: Srikumar P. Chellappan Copyright © 2019 Yanfang Wang et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Introduction. Gliomas are infltrative neoplasms of a highly invasive nature. Diferent stages of gliomas feature distinct genomic, genetic, and epigenetic changes. Te long noncoding RNA Growth Arrest Specifc Transcript 5 (GAS5) is an identifed tumour suppressor involved in several cancers. However, the underlying roles of the GAS5 gene in lower-grade glioma (LGG) patients are not clear. Methods. Via bioinformatic analysis based on TCGA-LGG and TCGA-GBM data, we explored the mechanisms of GAS5 expression in LGG (grades II and III) and high-grade glioma (glioblastoma multiforme, grade IV). Te log-rank test and multivariate Cox analysis were performed to fnd the association between GAS5 and overall survival (OS) in LGG patients. Weighted gene coexpression network analysis (WGCNA) and RNA-Seq analysis were applied to fnd the key gene network associated with GAS5. Results. We found that GAS5 expression was downregulated in both LGG and glioblastoma multiforme (GBM) compared with normal brain tissue. Low methylation in the GAS5 promoter region was detected in both LGG and GBM tissues. Te amplifcation type was the predominant type of GAS5 gene alteration in both LGG and GBM. High GAS5 expression was more associated with long overall survival (OS) in LGG patients than in GBM patients. Te multivariate survival analysis of GAS5 and clinical and molecular characteristics in LGG patients further confrmed the association between GAS5 and OS in LGG patients. We then developed a nomogram for clinical use. WGCNA and RNA-Seq analysis indicated that ribosomal biogenesis and translation initiation were the predominant events regulated by GAS5 in LGG patients. Conclusion. Taken together, these results demonstrate that GAS5 expression is associated with OS in LGG patients and that its underlying roles involve the regulation of ribosomal biogenesis and translation initiation, which may aid in identifying a new target for the treatment of LGG. 1. Introduction children with central nervous system (CNS) neoplasms, and no efective therapies currently exist [5]. In most cases, Gliomas are commonly classifed as low-grade glioma (LGG, GBM will recur afer surgical resection, resulting in a poor grades II and III) or glioblastoma multiforme (GBM, grade prognosis. Hundreds of molecular alterations exist in LGG IV). LGGs are infltrative neoplasms that arise most ofen and GBM, making them react diferently to chemotherapy, in the cerebral hemispheres of adults, including oligoden- radiotherapy, and surgical resection. Identifying the key drogliomas, oligoastrocytomas, and astrocytomas [1]. A sub- genes or genome alterations that drive the progression of set of LGGs progress into GBM within a few months, and gliomas will contribute to the understanding of the molecular others may stay stable for several years, causing large varia- mechanism behind gliomas and help to improve the efects of tions in median survival [2, 3]. Hence, individual treatments therapy. should be performed based on the identifcation of histologic Long noncoding RNAs (lncRNAs) are non-protein- class, grade, and reactions to chemotherapy and radiotherapy coding transcripts that play essential roles in cellular regu- [4]. GBM is the most common cause of death among lation at various levels and in diverse biological functions, 2 Journal of Oncology including chromatin modifcation, transcriptional regula- Te salmon and blue modules, which had most signifcant tion, cell diferentiation, immune responses, and epigenetic adjusted p-values, were selected. Genes involved in the regulation [6–8]. GAS5 produces a spliced lncRNA, which salmon and blue modules and their weights as calculated by sensitizes cells to apoptosis by suppressing glucocorticoid- WGCNA were visualized by Cytoscape 3.4.0 [21]. GO analysis mediated induction of several responsive genes [9]. By was performed using the clusterProfler package [22] and binding to the DNA-binding domain of the glucocorticoid Metascape (http://metascape.org/gp/index.html) [23]. Gene receptor, GAS5 acts as a decoy glucocorticoid response ele- set enrichment analysis (GSEA) was applied by the GSEA ment (GRE), thus competing with DNA GREs to bind to the sofware from Broad Institute [24]. glucocorticoid receptor [9]. By analysing GAS5 level and clin- ical parameters, it has been found that GAS5 correlates with 2.3. Statistical Analysis. Statistical analysis was performed tumour progression and poor prognosis in many tumour using R (R: A language and environment for statistical types [10–13]. Some publications have also indicated that computing. R Foundation for Statistical Computing, Vienna, GAS5 is a predictor of survival in GBM patients [14, 15]. One Austria. URL http://www.R-project.org/). Te association study revealed an association between serum GAS5 level and between GAS5 expression and the clinicopathological fea- the OS of GBM patients [14]. However, the potential roles of tures was evaluated by the diferent mathematical methods GAS5 involvement in gliomas and the regulatory mechanism listed in the table [25]. Te log-rank test was performed to of GAS5 expression in gliomas are not clearly identifed. assess the diference between the Kaplan-Meier curves. Te Besides, the diference of GAS5 expression and the regulatory fold change and Q value for samples with high and low GAS5 mechanism of GAS5 expression in LGG and GBM patients expression were calculated using the limma package [26]. A have not been shown yet. In this study, via bioinformatic Qvalue< 0.05 was considered statistically signifcant. analysis, we explored the regulatory mechanisms of GAS5 expression in gliomas and compared its prognostic value in 3. Results LGG and GBM. In addition, based on TCGA-LGG RNA-Seq datasets, we also applied WGCNA and enrichment analysis 3.1. GAS5 Was Upregulated in Both LGG and GBM Compared to identify the pathways highly associated with GAS5 in LGG with Normal Brain Tissues. GAS5 expression levels were and the network of genes highly associated with GAS5. characterized in several types of solid tumours, including LGG and GBM (Figure 1). Te results indicated that GAS5 2. Materials and Methods was downregulated in both LGG and GBM tissue com- pared with the normal brain tissue. Ten, we compared the 2.1. Clinical and Omic Data Download. RNA-Seq and DNA expression level of GAS5 between LGG and GBM (Figures methylation datasets from patients with primary LGG or 2(a), 2(b), and S1a). No signifcant diference was identifed GBM were downloaded from the UCSC Xena browser between the LGG and GBM datasets. In addition, grade II, (https://xenabrowser.net/) [16]. GAS5 mRNA expressions grade III, and grade IV gliomas had similar expression levels in diferent types of solid tumours and in corresponding of GAS5, which were all higher than that of normal brain normal tissues were obtained from TCGA datasets and GTEx tissues. Te DNA methylation level of GAS5 was analysed datasets [17]. A box plot was created using ggplot2 [18]. by DNA methylation 450K chips, and the six probes were chosen from the CpG island in the promoter region of GAS5. All probes showed low � values (<0.1), and there 2.2. WGCNA of RNA-Seq Data from LGG Patients and � Network Visualization. Te WGCNA R package was used were no diferences in values from any of the six probes to evaluate the correlation of GAS5 expression and module between LGG and GBM tissues, indicating low methylation membership by the ‘p.weighted’ function [19]. An adjacency of the GAS5 promoter in both LGG and GBM patients matrix was generated to evaluate the weighted coexpression (Figure 2(c)). Te association between GAS5 methylation values between all the subjects in the probe set. Te coex- and GAS5 expression was tested, revealing no signifcant relationship in either GBM or LGG tissues (Figures S1B and pression similarity ��,� wasdefnedastheabsolutevalueofthe correlation coefcient between the profles of nodes � and �: S1C). Ten, to investigate the driver of high GAS5 expression in LGG and GBM tissues, we also examined copy number � � � � alterations (CNAs) in LGG and GBM (Figures 2(d) and 2(e)). ��,� = ���� (��,��)� (1) Te results showed that the amplifcation-type alteration where �� and �� were expression value of for genes � and � and contributed to the high expression of GAS5 in both LGG and ��,� represented Pearson’s correlation coefcient of gene � and GBM tissues (P = 0.044 and P = 0.047). gene �. A weighed network adjacency was defned by raising the 3.2.LowGAS5ExpressionWasaPredictorofPoorSurvival coexpression similarity to a power �: in LGG. Te associations between GAS5 expression and the pathological parameters of patients with primary LGG and � ��,� =��,� (2) GBM were summarized in Table 1. In patients with LGG, higher GAS5 expression was signifcantly correlated with with �≥1[20]. We selected the power of � =4and higher tumour purity (Table 1 and Figure S2). Nevertheless, 2 scale free R = 0.95 as the sof-thresholding parameter we could not fnd a similar tendency in patients with GBM. to ensure a signed scale-free coexpression gene network.
Load more

Recommended publications
  • Micrornas Mediated Regulation of the Ribosomal Proteins and Its Consequences on the Global Translation of Proteins
    cells Review microRNAs Mediated Regulation of the Ribosomal Proteins and Its Consequences on the Global Translation of Proteins Abu Musa Md Talimur Reza 1,2 and Yu-Guo Yuan 1,3,* 1 Jiangsu Co-Innovation Center of Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China; [email protected] 2 Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawi´nskiego5a, 02-106 Warsaw, Poland 3 Jiangsu Key Laboratory of Zoonosis/Joint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou 225009, China * Correspondence: [email protected]; Tel.: +86-514-8797-9228 Abstract: Ribosomal proteins (RPs) are mostly derived from the energy-consuming enzyme families such as ATP-dependent RNA helicases, AAA-ATPases, GTPases and kinases, and are important structural components of the ribosome, which is a supramolecular ribonucleoprotein complex, composed of Ribosomal RNA (rRNA) and RPs, coordinates the translation and synthesis of proteins with the help of transfer RNA (tRNA) and other factors. Not all RPs are indispensable; in other words, the ribosome could be functional and could continue the translation of proteins instead of lacking in some of the RPs. However, the lack of many RPs could result in severe defects in the biogenesis of ribosomes, which could directly influence the overall translation processes and global expression of the proteins leading to the emergence of different diseases including cancer. While microRNAs (miRNAs) are small non-coding RNAs and one of the potent regulators of the post-transcriptional 0 gene expression, miRNAs regulate gene expression by targeting the 3 untranslated region and/or coding region of the messenger RNAs (mRNAs), and by interacting with the 50 untranslated region, Citation: Reza, A.M.M.T.; Yuan, Y.-G.
    [Show full text]
  • History of the Ribosome and the Origin of Translation
    History of the ribosome and the origin of translation Anton S. Petrova,1, Burak Gulena, Ashlyn M. Norrisa, Nicholas A. Kovacsa, Chad R. Berniera, Kathryn A. Laniera, George E. Foxb, Stephen C. Harveyc, Roger M. Wartellc, Nicholas V. Huda, and Loren Dean Williamsa,1 aSchool of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332; bDepartment of Biology and Biochemistry, University of Houston, Houston, TX, 77204; and cSchool of Biology, Georgia Institute of Technology, Atlanta, GA 30332 Edited by David M. Hillis, The University of Texas at Austin, Austin, TX, and approved November 6, 2015 (received for review May 18, 2015) We present a molecular-level model for the origin and evolution of building up of the functional centers, proceeds to the establishment the translation system, using a 3D comparative method. In this model, of the common core, and continues to the development of large the ribosome evolved by accretion, recursively adding expansion metazoan rRNAs. segments, iteratively growing, subsuming, and freezing the rRNA. Incremental evolution of function is mapped out by stepwise Functions of expansion segments in the ancestral ribosome are accretion of rRNA. In the extant ribosome, specific segments of assigned by correspondence with their functions in the extant rRNA perform specific functions including peptidyl transfer, ribosome. The model explains the evolution of the large ribosomal subunit association, decoding, and energy-driven translocation subunit, the small ribosomal subunit, tRNA, and mRNA. Prokaryotic (11). The model assumes that the correlations of rRNA segments ribosomes evolved in six phases, sequentially acquiring capabilities with their functions have been reasonably maintained over the for RNA folding, catalysis, subunit association, correlated evolution, broad course of ribosomal evolution.
    [Show full text]
  • Structures and Stabilization of Kinetoplastid-Specific Split Rrnas Revealed by Comparing Leishmanial and Human Ribosomes
    ARTICLE Received 7 Jun 2016 | Accepted 13 Sep 2016 | Published 18 Oct 2016 DOI: 10.1038/ncomms13223 OPEN Structures and stabilization of kinetoplastid-specific split rRNAs revealed by comparing leishmanial and human ribosomes Xing Zhang1,2,*, Mason Lai3,*, Winston Chang3, Iris Yu3, Ke Ding3, Jan Mrazek4,HweeL.Ng4, Otto O. Yang2,4, Dmitri A. Maslov5 & Z. Hong Zhou2,3 The recent success in ribosome structure determination by cryoEM has opened the door to defining structural differences between ribosomes of pathogenic organisms and humans and to understand ribosome-targeting antibiotics. Here, by direct electron-counting cryoEM, we have determined the structures of the Leishmania donovani and human ribosomes at 2.9 Å and 3.6 Å, respectively. Our structure of the leishmanial ribosome elucidates the organization of the six fragments of its large subunit rRNA (as opposed to a single 28S rRNA in most eukaryotes, including humans) and reveals atomic details of a unique 20 amino acid extension of the uL13 protein that pins down the ends of three of the rRNA fragments. The structure also fashions many large rRNA expansion segments. Direct comparison of our human and leishmanial ribosome structures at the decoding A-site sheds light on how the bacterial ribosome-targeting drug paromomycin selectively inhibits the eukaryotic L. donovani, but not human, ribosome. 1 Center of Cryo Electron Microscopy, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China. 2 California NanoSystems Institute, University of California, Los Angeles, California 90095, USA. 3 Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, California 90095, USA. 4 Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095, USA.
    [Show full text]
  • HUMAN RIBOSOME BIOGENESIS and the REGULATION of the TUMOUR SUPPRESSOR P53
    HUMAN RIBOSOME BIOGENESIS AND THE REGULATION OF THE TUMOUR SUPPRESSOR p53 Andria Pelava Submitted for Doctor of Philosophy Final submission: December 2016 Institute of Cell and Molecular Biosciences Faculty of Medical Sciences Newcastle University ii Abstract Ribosome production is an energetically expensive and, therefore, highly regulated process. Defects in ribosome biogenesis lead to genetic diseases called Ribosomopathies, such as Dyskeratosis Congenita (DC), and mutations in ribosomal proteins and ribosome biogenesis factors are linked to multiple types of cancer. During ribosome biogenesis, the ribosomal RNAs (rRNAs) are processed and modified, and defects in ribosome biogenesis lead to the activation of p53. This project aimed to investigate the functions of Dyskerin, mutated in X-linked DC, in human ribosome biogenesis and p53 regulation, and to explore the link between ribosome production and p53 homeostasis. Dyskerin is an rRNA pseudouridine synthase and required for telomere maintenance. There is some debate as to whether DC is the result of telomere maintenance or ribosome biogenesis defects. It is shown here that human Dyskerin is required for the production of both LSU and SSU, and knockdown of Dyskerin leads to p53 activation via inhibition of MDM2 via the 5S RNP, an LSU assembly intermediate which accumulates after ribosome biogenesis defects. My data indicate that p53 activation, due to defects in ribosome biogenesis, may contribute to the clinical symptoms seen in patients suffering with DC. In addition, it is shown that defects in early or late stages of SSU or LSU biogenesis, result in activation of p53 via the 5S RNP-MDM2 pathway, and that p53 is induced in less than 12 hours after ribosome biogenesis defects.
    [Show full text]
  • Fanconi Anemia Protein FANCI Functions in Ribosome Biogenesis
    Fanconi anemia protein FANCI functions in ribosome biogenesis Samuel B. Sondallea, Simonne Longerichb,1, Lisa M. Ogawab, Patrick Sungb,c, and Susan J. Basergaa,b,c,2 aDepartment of Genetics, Yale School of Medicine, New Haven, CT 06520; bDepartment of Molecular Biophysics and Biochemistry, Yale School of Medicine, New Haven, CT 06520; and cDepartment of Therapeutic Radiology, Yale School of Medicine, New Haven, CT 06520 Edited by Joseph G. Gall, Carnegie Institution of Washington, Baltimore, MD, and approved December 28, 2018 (received for review July 8, 2018) Fanconi anemia (FA) is a disease of DNA repair characterized by bone responsible for the transcription of pre-ribosomal RNA (pre- marrow failure and a reduced ability to remove DNA interstrand rRNA) (33). The clear phenotypic overlap between FA and cross-links. Here, we provide evidence that the FA protein FANCI also bone marrow failure ribosomopathies and the connection between functions in ribosome biogenesis, the process of making ribosomes BRCA1 (FANCS) and RNAPI suggest a possible connection be- that initiates in the nucleolus. We show that FANCI localizes to the tween FA and defects in ribosome biogenesis. nucleolus and is functionally and physically tied to the transcription The process of making ribosomes in eukaryotes, termed ri- of pre-ribosomal RNA (pre-rRNA) and to large ribosomal subunit bosome biogenesis, initiates in the large nonmembrane-bound (LSU) pre-rRNA processing independent of FANCD2. While FANCI is nuclear organelle, the nucleolus (NO) (34, 35). In the NO, tan- known to be monoubiquitinated when activated for DNA repair, we dem repeats of ribosomal DNA (rDNA) (36) are transcribed by find that it is predominantly in the deubiquitinated state in the RNAPI, which generates a long pre-rRNA (37).
    [Show full text]
  • Transcriptomic Regulation of Alternative Phenotypic Trajectories in Embryos of the Annual Killifish Austrofundulus Limnaeus
    Portland State University PDXScholar Dissertations and Theses Dissertations and Theses Fall 11-30-2017 Transcriptomic Regulation of Alternative Phenotypic Trajectories in Embryos of the Annual Killifish Austrofundulus limnaeus Amie L. Romney Portland State University Follow this and additional works at: https://pdxscholar.library.pdx.edu/open_access_etds Part of the Biology Commons, and the Genetics and Genomics Commons Let us know how access to this document benefits ou.y Recommended Citation Romney, Amie L., "Transcriptomic Regulation of Alternative Phenotypic Trajectories in Embryos of the Annual Killifish Austrofundulus limnaeus" (2017). Dissertations and Theses. Paper 4033. https://doi.org/10.15760/etd.5917 This Dissertation is brought to you for free and open access. It has been accepted for inclusion in Dissertations and Theses by an authorized administrator of PDXScholar. Please contact us if we can make this document more accessible: [email protected]. Transcriptomic Regulation of Alternative Phenotypic Trajectories in embryos of the Annual Killifish Austrofundulus limnaeus by Amie Lynn Thomas Romney A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biology Dissertation Committee Jason Podrabsky, Chair Suzanne Estes Bradley Buckley Todd Rosenstiel Dirk Iwata-Reuyl Portland State University 2017 © 2017 Amie Lynn Thomas Romney ABSTRACT The Annual Killifish, Austrofundulus limnaeus, survives the seasonal drying of their pond habitat in the form of embryos entering diapause midway through development. The diapause trajectory is one of two developmental phenotypes. Alternatively, individuals can “escape” entry into diapause and develop continuously until hatching. The alternative phenotypes of A. limnaeus are a form of developmental plasticity that provides this species with a physiological adaption for surviving stressful environments.
    [Show full text]
  • Supersized Ribosomal RNA Expansion Segments in Asgard Archaea 2 Authors: Petar I
    bioRxiv preprint doi: https://doi.org/10.1101/2019.12.25.888164; this version posted June 13, 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. 1 Supersized ribosomal RNA expansion segments in Asgard archaea 2 Authors: Petar I. Penev1,2, Sara Fakhretaha-Aval1,3, Vaishnavi J. Patel4, Jamie J. Cannone4, 3 Robin R. Gutell4, Anton S. Petrov1,3*, Loren Dean Williams1,2,3*, Jennifer B. Glass1,2,5* 4 Affiliations: 1NASA Center for the Origin of Life, Georgia Institute of Technology, Atlanta, GA 30332-0400, USA 2School of Biological Sciences, Georgia Institute of Technology, North Avenue, Atlanta, GA 30332, USA 3School of Chemistry and Biochemistry, Georgia Institute of Technology, 901 Atlantic Dr, Atlanta, GA 30332, USA 5 4Department of Integrative Biology, The University of Texas at Austin, 2415 Speedway #C0930, 6 Austin, TX 78712, USA 7 5School of Earth and Atmospheric Sciences, Georgia Institute of Technology, 311 Ferst Dr, 8 Atlanta, GA 30332, USA 9 *Correspondence to: [email protected]; [email protected]; 10 [email protected] 11 1 bioRxiv preprint doi: https://doi.org/10.1101/2019.12.25.888164; this version posted June 13, 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.
    [Show full text]
  • Structures and Stabilization of Kinetoplastid-Specific Split Rrnas
    ARTICLE Received 7 Jun 2016 | Accepted 13 Sep 2016 | Published 18 Oct 2016 DOI: 10.1038/ncomms13223 OPEN Structures and stabilization of kinetoplastid-specific split rRNAs revealed by comparing leishmanial and human ribosomes Xing Zhang1,2,*, Mason Lai3,*, Winston Chang3, Iris Yu3, Ke Ding3, Jan Mrazek4,HweeL.Ng4, Otto O. Yang2,4, Dmitri A. Maslov5 & Z. Hong Zhou2,3 The recent success in ribosome structure determination by cryoEM has opened the door to defining structural differences between ribosomes of pathogenic organisms and humans and to understand ribosome-targeting antibiotics. Here, by direct electron-counting cryoEM, we have determined the structures of the Leishmania donovani and human ribosomes at 2.9 Å and 3.6 Å, respectively. Our structure of the leishmanial ribosome elucidates the organization of the six fragments of its large subunit rRNA (as opposed to a single 28S rRNA in most eukaryotes, including humans) and reveals atomic details of a unique 20 amino acid extension of the uL13 protein that pins down the ends of three of the rRNA fragments. The structure also fashions many large rRNA expansion segments. Direct comparison of our human and leishmanial ribosome structures at the decoding A-site sheds light on how the bacterial ribosome-targeting drug paromomycin selectively inhibits the eukaryotic L. donovani, but not human, ribosome. 1 Center of Cryo Electron Microscopy, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China. 2 California NanoSystems Institute, University of California, Los Angeles, California 90095, USA. 3 Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, California 90095, USA. 4 Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095, USA.
    [Show full text]
  • The ¢Rst Determination of Pseudouridine Residues in 23S
    FEBS Letters 462 (1999) 94^100 FEBS 22957 CORE Metadata, citation and similar papers at core.ac.uk Provided byThe Elsevier - Publisher ¢rst Connector determination of pseudouridine residues in 23S ribosomal RNA from hyperthermophilic Archaea Sulfolobus acidocaldarius Se¨verine Massenet1, Isabelle Ansmant1, Yuri Motorin, Christiane Branlant* Laboratoire de Maturation des ARN et Enzymologie Mole¨culaire, UMR 7567 CNRS-UHP Nancy I, Faculte¨ des Sciences, P.O. Box 239, 54506 Vandoeuvre-les-Nancy Cedex, France Received 16 October 1999 sites present in LSU rRNAs are evolutionarily conserved. The Abstract We describe the first identification of pseudouridine (8) residues in ribosomal RNA (23S rRNA) of an hyperthermo- situation is quite di¡erent for the 8 residues present in the philic Archaea Sulfolobus acidocaldarius. In contrast to Eucarya rRNA of the small ribosomal subunit (SSU). In this rRNA, rRNA, only six 8 residues were detected, which is rather close to the 8 residues are mostly present at sites speci¢c for each the situation in Bacteria. However, three modified positions organism and no apparent clustering of these modi¢ed nucleo- (82479, 82535 and 82550) are unique for S. acidocaldarius. Two 8 tides in de¢ned areas of SSU rRNA was observed (for review residues at positions 2060 and 2594 are universally conserved, see [2]) while one other 8 (position 2066) is also common to Eucarya. Synthesis of 8 residues in RNA molecules is catalysed by a Taken together the results argue against the conservation of 8- large family of enzymes, the RNA:8-synthases. Recent prog- synthases between Archaea and Bacteria and provide a basis for ress in studies of 8 residue formation demonstrated that Bac- the search of snoRNA-like guides for 8 formation in Archaea.
    [Show full text]
  • Analysis of Subunit Folding Contribution of Three Yeast Large Ribosomal
    bioRxiv preprint doi: https://doi.org/10.1101/2021.05.18.444632; this version posted May 18, 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 4.0 International license. 1 Analysis of subunit folding contribution of three yeast large 2 ribosomal subunit proteins required for stabilisation and 3 processing of intermediate nuclear rRNA precursors. 4 5 6 7 Gisela Pöll1, Michael Pilsl2, Joachim Griesenbeck1*, Herbert Tschochner1*, Philipp 8 Milkereit1* 9 10 11 12 1 Chair of Biochemistry III, Regensburg Center for Biochemistry, University of 13 Regensburg, Regensburg, Germany 14 15 2 Structural Biochemistry Unit, Regensburg Center for Biochemistry, University of 16 Regensburg, Regensburg, Germany 17 18 * Corresponding authors 19 [email protected] 20 [email protected] 21 [email protected] 22 23 24 25 26 Abstract 27 28 In yeast and human cells many of the ribosomal proteins (r-proteins) are required for 29 the stabilisation and productive processing of rRNA precursors. Functional coupling 30 of r-protein assembly with the stabilisation and maturation of subunit precursors 31 potentially promotes the production of ribosomes with defined composition. To further 32 decipher mechanisms of such an intrinsic quality control pathway we analysed here 33 the contribution of three yeast large ribosomal subunit r-proteins for intermediate 34 nuclear subunit folding steps. Structure models obtained from single particle cryo- 35 electron microscopy analyses provided evidence for specific and hierarchic effects on 36 the stable positioning and remodelling of large ribosomal subunit domains.
    [Show full text]
  • Supplementary Information Heterogeneity and Interplay of The
    Supplementary Information Heterogeneity and interplay of the extracellular vesicle small RNA transcriptome and proteome Helena Sork, Giulia Corso, Kaarel Krjutskov, Henrik J. Johansson, Joel Z. Nordin, Oscar P.B. Wiklander, Yi Xin Fiona Lee, Jakub Orzechowski Westholm, Janne Lehtiö, Matthew J.A. Wood, Imre Mäger, Samir EL Andaloussi cells EVs cells EVs ALIX (96 kDa) TSG101 (50 kDa) cells EVs cells EVs Calnexin (75 kDa) SDCBP (32 kDa) cells EVs ß-actin (42 kDa) Supplementary Figure S1. Uncropped western blot images of cell- and EV samples. Cropped images can be found in Figure 1a. SDCBP (syntenin, human reactive antibody). 17-35nt RNA sequences ❶ ‘small RNA’ annotation a) miRNA. piRNA. snRNA. and snoRNA b) No feature ❷ ‘rRNA’ annotation a) LSU/SSU rRNA. Mt_rRNA. predicted rRNA (MMu). rRNA pseudogenes (HSa) b) No feature ❸ ‘other RNA’ annotation a) tRNA. Mt_tRNA. protein coding genes. lncRNA. misc_RNA. proc_transcripts. pseudogenes and scRNA b) No feature Supplementary Figure S2. Annotation of small RNA sequencing data. All mapped reads in the size range of 17–35 nt reads were annotated against the respective human or mouse ‘small RNA’ genomic features (gene biotypes according to Vega, version 68 ). The reads with no found ‘small RNA’ feature were filtered out and subjected to ’rRNA’ annotation. Finally, all reads that did not match ‘small RNA’ or ‘rRNA’ were annotated against the custom-compiled list of ‘other RNA’ annotations. LSU/SSU rRNA – large/small subunit ribosomal RNA; Mt_rRNA – mitochondrial ribosomal RNA; misc_RNA – miscalleous
    [Show full text]
  • View / Open Frantz Oregon 0171N 12802.Pdf
    OVARIAN TRANSCRIPTOMICS OF D. MELANOGASTER REVEAL CANDIDATE GENES UNDERLYING WOLBACHIA-ASSOCIATED PLASTIC RECOMBINATION by SOPHIA I FRANTZ A THESIS Presented to the Department of Biology and the Graduate School of the University of Oregon in partial fulfillment of the requirements for the degree of Master of Science June 2020 THESIS APPROVAL PAGE Student: Sophia I Frantz Title: Ovarian Transcriptomics of D. melanogaster Reveal Candidate Genes Underlying Wolbachia-Associated Plastic Recombination This thesis has been accepted and approved in partial fulfillment of the requirements for the Master of Science degree in the Department of Biology by: Dr. Nadia Singh Chairperson Dr. William Cresko Chairperson Dr. Peter Ralph Member and Kate Mondloch Interim Vice Provost and Dean of the Graduate School Original approval signatures are on file with the University of Oregon Graduate School. Degree awarded June 2020 ii © 2020 Sophia I Frantz iii THESIS ABSTRACT Sophia I Frantz Master of Science Department of Biology June 2020 Title: Ovarian Transcriptomics of D. melanogaster Reveal Candidate Genes Underlying Wolbachia-Associated Plastic Recombination Phenotypic plasticity is prevalent in nature, and its study facilitates understanding of how organisms acclimate to stressful environments. Recombination rate is plastic in a diversity of organisms and under a variety of stressful conditions. However, the recent finding that Wolbachia pipientis induces plastic recombination in Drosophila melanogaster deviates from previous patterns, because Wolbachia is not strictly considered a stressor to this host. We investigate the molecular mechanisms of Wolbachia-associated plastic recombination by comparing the ovarian transcriptomes of D. melanogaster infected and uninfected with Wolbachia. Our data suggest infection explains a small amount of transcriptional variation but specifically affects genes related to cell cycle, translation, and metabolism.
    [Show full text]