DOCSLIB.ORG

Selective Role of the Translin/Trax Rnase Complex in Hippocampal Synaptic Plasticity Alan Jung Park1,5*†, Mahesh Shivarama Shetty2,3†, Jay M

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Selective Role of the Translin/Trax Rnase Complex in Hippocampal Synaptic Plasticity Alan Jung Park1,5*†, Mahesh Shivarama Shetty2,3†, Jay M Park et al. Mol Brain (2020) 13:145 https://doi.org/10.1186/s13041-020-00691-5 RESEARCH Open Access Selective role of the translin/trax RNase complex in hippocampal synaptic plasticity Alan Jung Park1,5*†, Mahesh Shivarama Shetty2,3†, Jay M. Baraban4 and Ted Abel1,2,3* Abstract Activity-dependent local protein synthesis is critical for synapse-specifc, persistent plasticity. Abnormalities in local protein synthesis have been implicated in psychiatric disorders. We have recently identifed the translin/trax micro- RNA-degrading enzyme as a novel mediator of protein synthesis at activated synapses. Additionally, translin knockout (KO) mice, which lack translin/trax, exhibit some of the behavioral abnormalities found in a mouse model of fragile X syndrome (fragile X mental retardation protein-FMRP-KO mice). Therefore, identifying signaling pathways interact- ing with translin/trax to support persistent synaptic plasticity is a translationally relevant goal. Here, as a frst step to achieve this goal, we have assessed the requirement of translin/trax for multiple hippocampal synaptic plasticity paradigms that rely on distinct molecular mechanisms. We found that mice lacking translin/trax exhibited selective impairment in a form of persistent hippocampal plasticity, which requires postsynaptic protein kinase A (PKA) activ- ity. In contrast, enduring forms of plasticity that are dependent on presynaptic PKA were unafected. Furthermore, these mice did not display exaggerated metabotropic glutamate receptor-mediated long-term synaptic depression (mGluR-LTD), a hallmark of the FMRP KO mice. On the contrary, translin KO mice exhibited defcits in N-methyl-D-as- partate receptor (NMDAR) dependent LTD, a phenotype not observed in the FMRP knockouts. Taken together, these fndings demonstrate that translin/trax mediates long-term synaptic plasticity that is dependent on postsynaptic PKA signaling and suggest that translin/trax and FMRP play distinct roles in hippocampal synaptic plasticity. Keywords: Translin, Trax, Long-term potentiation, Long-term depression, Local protein synthesis, Hippocampal synaptic plasticity, FMRP, RNA-binding protein, microRNA, PKA Introduction 3, 5]. Several RNA-binding proteins (RBPs) take part in Extensive evidence suggests that localization of key the trafcking and translational regulation of specifc mRNAs in the vicinity of synapses and activity-medi- mRNAs and thus allowing diversity in the mechanisms ated regulation of their translation contributes to per- engaged by diferent forms of plasticity [6–8]. Te RNA- sistent forms of synaptic plasticity related to long-term binding protein translin is an evolutionarily conserved memory [1–4]. Tis synapse-specifc, activity-dependent brain-enriched protein, which regulates RNA trafck- mechanism requires precisely regulated molecular sign- ing and translational control [9–12]. Together with its aling in presynaptic or postsynaptic compartments [2, partner protein, translin-associated factor X (trax), these proteins form a microRNA-degrading enzyme that *Correspondence: [email protected]; [email protected] can trigger protein synthesis by reversing microRNA- †Alan Jung Park and Mahesh Shivarama Shetty have contributed equally mediated silencing [13–15]. We have previously shown 1 Department of Biology, University of Pennsylvania, Philadelphia, PA, USA that the translin/trax RNase complex mediates activity- 5 Present Address: Gogos Lab, Mortimer B. Zuckerman Mind Brain Behavior Institute, Jerome L. Greene Science Center, Columbia University, dependent local synaptic protein synthesis required for L5-053, 3227 Broadway, New York, NY 10027, USA input-specifc heterosynaptic plasticity (synaptic tagging Full list of author information is available at the end of the article and capture) and memory formation [15]. However, the © The Author(s) 2020, corrected publication 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creat iveco mmons .org/licen ses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creat iveco mmons .org/publi cdoma in/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Park et al. Mol Brain (2020) 13:145 Page 2 of 9 mechanisms that regulate translin/trax activity within glutamate receptors (mGluRs), was freshly prepared as a synaptic compartments have not been investigated. 10 mM solution in milliQ water and delivered at 100 μM Our previous fndings suggest that translin/trax may fnal concentration in aCSF as previously described [23]. interact with the cAMP-PKA signaling pathway. Specif- cally, the microRNA targets of translin/trax are predicted Electrophysiology to regulate the expression of PKA-anchoring proteins, Experiments were performed as described [15]. Briefy, cAMP-degrading phosphodiesterases (PDEs), cAMP- both male and female 2–5-month-old mice (4–6 weeks producing Gs-coupled β2-adrenergic receptors and old for LTD) were sacrifced by cervical dislocation adenylyl cyclases [15]. In fact, the cAMP-PKA signaling and hippocampi were quickly collected in chilled, oxy- pathway is highly localized within presynaptic or post- genated aCSF (124 mM NaCl, 4.4 mM KCl, 1.3 mM synaptic compartments by PKA-anchoring proteins and MgSO4⋅7H2O, 1 mM NaH2PO4⋅H2O, 26.2 mM NaHCO3, mediates protein synthesis required for persistent synap- 2.5 mM CaCl2⋅2H2O and 10 mM d-glucose) bubbled with tic plasticity and memory formation [16–20]. Terefore, 95% O2/5% CO2. 400 μm-thick transverse hippocampal investigating whether translin/trax interacts with PKA slices were prepared using a manual slicer (Stoelting) signaling within presynaptic or postsynaptic compart- and placed in an interface recording chamber at 28 °C ments can provide clues to understanding molecular (Fine Science Tools, Foster City, CA). Te slices were mechanisms linking translin/trax to synaptic plasticity constantly perfused with aCSF at 1 ml/min (or 2.5 ml/ and memory formation. min for the mGluR-LTD experiment). Slices were equili- In the present study, we determined the role of trans- brated for at least 2 h in aCSF. All the recordings were lin/trax in distinct forms of synaptic plasticity, which performed in the Schafer collateral synapses in the CA1 require presynaptic or postsynaptic PKA signaling. As stratum radiatum. Te stimulus intensity was set to trax protein is unstable in the absence of translin, in the elicit ~ 40% of the maximum feld-EPSP amplitude deter- current study we used translin KO mice, which lack both mined by an input–output curve in each experiment. translin and trax proteins [15, 21]. Te frst 20-min baseline values were averaged, and the average was used to normalize each initial fEPSP slope. Materials and methods Te input–output relationship was measured as previ- All experiments were performed according to the ously described [15]. To electrically induce long-term National Institutes of Health guidelines and were fully potentiation (LTP), spaced 4-train (four 1 s 100 Hz trains approved by the Institutional Animal Care and Use Com- delivered 5 min apart), massed 4-train (four 1 s 100 Hz mittee at the University of Pennsylvania and at the Uni- trains delivered 5 s apart), theta-burst stimulation (TBS, versity of Iowa. 15 bursts of four 100 Hz pulses delivered for a total of 3 s at 5 Hz), and one-train (one 1 s 100 Hz train) stimula- Translin knockout (KO) mice tion were delivered after 20 min baseline recordings. To Te generation and maintenance of translin KO mice chemically induce LTP, 50 μM of FSK in aCSF was bath (MGI: 2677496) were described previously [21, 22]. Mice applied to the slices for 15 min following 20-min base- were backcrossed to C57BL/6J for more than 15 genera- line recordings. To chemically induce LTD, 100 μM of tions. Heterozygous male and heterozygous female mice DHPG in aCSF was bath applied to the slices for 10 min were mated to produce homozygous translin KO mice following 20-min baseline recordings. For the NMDAR- and wildtype littermates. Mice were maintained on a 12 h LTD experiments, the stimulus intensity was set to light/12 h dark cycle with lights on at 8 am (ZT0). Food elicit ~ 50% of the maximal fEPSP amplitude determined and water were available ad libitum. All experiments were by an input–output curve in each experiment and LTD performed during the light cycle using translin KO mice was induced by a prolonged low-frequency stimulation and wildtype littermates as controls. 2- to 5-month-old (LFS) protocol (1 Hz, 15 min) [24, 25], following 20-min mice were used for all experiments except for the LTD baseline recordings. experiments in which 4- to 6-week-old mice were used. Western blotting Drugs Hippocampal tissue homogenization, protein separation Forskolin (FSK, Molecular grade, Sigma), an adenylyl and transfer to polyvinylidene difuoride (PVDF) mem- cyclase activator, was freshly prepared as a 50 mM solu- branes were performed as previously described [26]. tion in 100% ethanol and delivered at 50 μM fnal con- Membranes were blocked in 5% BSA or 5% non-fat milk centration in artifcial cerebrospinal fuid (aCSF) as in TBST and incubated with primary antibodies (trans- described before [19]. (RS)-3,5-Dihydroxyphenylglycine lin, 1:100,000; FMRP, 1:10,000, Millipore) overnight at (DHPG, Tocris), a potent agonist of group I metabotropic 4 °C.
Load more

Recommended publications
  • Regulation of RNA Interference Pathways in the Insect Vector Laodelphax Striatellus by Viral Proteins of Rice Stripe Virus
    viruses Article Regulation of RNA Interference Pathways in the Insect Vector Laodelphax striatellus by Viral Proteins of Rice Stripe Virus Yan Xiao 1,2,†, Qiong Li 1,3,†, Wei Wang 1, Yumei Fu 4 and Feng Cui 1,3,* 1 State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; [email protected] (Y.X.); [email protected] (Q.L.); [email protected] (W.W.) 2 College of Life Sciences, Hebei University, Baoding 071002, China 3 CAS Center for Excellence in Biotic Interactions, University of Chinese Academy of Sciences, Beijing 100049, China 4 Key Laboratory of Tropical Translational Medicine of Ministry of Education, School of Tropical Medicine and Laboratory Medicine, Hainan Medical University, Haikou 571199, China; [email protected] * Correspondence: [email protected] † These authors contributed equally to this work. Abstract: RNA interference (RNAi), especially the small interfering RNA (siRNA) and microRNA (miRNA) pathways, plays an important role in defending against viruses in plants and insects. However, how insect-transmitted phytoviruses regulate the RNAi-mediated antiviral response in vector insects has barely been uncovered. In this study, we explored the interaction between rice stripe virus (RSV) and the miRNA and siRNA pathways of the small brown planthopper, which is a vector insect. The transcript and protein levels of key genes in the two RNAi pathways did not change during the RSV infection process. When the expression of insect Ago1, Ago2, or Translin was silenced by the injection of double-stranded RNAs targeting these genes, viral replication was Citation: Xiao, Y.; Li, Q.; Wang, W.; promoted with Ago2 silencing but inhibited with Translin silencing.
    [Show full text]
  • Genomic Structure and Chromosomal Localization of the Gene Encoding TRAX, a Translin-Associated Factor X
    J Hum Genet (2000) 45:305–308 © Jpn Soc Hum Genet and Springer-Verlag 2000 SHORT COMMUNICATION Gaoyuan Meng · Katsunori Aoki · Katsunobu Tokura Kazuhiko Nakahara · Johji Inazawa · Masataka Kasai Genomic structure and chromosomal localization of the gene encoding TRAX, a Translin-associated factor X Received: May 30, 2000 / Accepted: July 26, 2000 Abstract The TRAX gene encodes a Translin-associated Introduction 33-kDa protein partner, TRAX. The TRAX protein has extensive amino acid homology with Translin, and contains bipartite nuclear targeting sequences, suggesting a possible We have previously identified the Translin-associated pro- role in the selective nuclear transport of Translin lacking tein X, TRAX (Aoki et al. 1997a), a novel protein of 290 any nuclear targeting motifs. In the present study, genomic amino acids with a predicted molecular mass of 33kDa, clones of the human TRAX gene were isolated to determine using a yeast two-hybrid system. Translin itself was origi- the complete genomic organization. The genomic structure nally identified as a DNA binding protein that specific- of the human TRAX gene was similar to that of the human ally recognized the consensus sequences found at the Translin gene, consisting of six exons and five introns, breakpoints of chromosomal translocations in many cases encompassing approximately 27kb in genomic DNA. of lymphoid neoplasms (Kasai et al. 1992; 1994; Aoki et al. Northern blot analysis revealed a predominant transcript 1994; 1995). Electron microscopic and crystallographic in- of approximately 2.7kb, and its distribution in various tis- vestigations have revealed that Translin is a ring-shaped sues was like that of Translin.
    [Show full text]
  • Translin and Trax Differentially Regulate Telomere-Associated Transcript Homeostasis
    www.impactjournals.com/oncotarget/ Oncotarget, Vol. 7, No. 23 Translin and Trax differentially regulate telomere-associated transcript homeostasis Natalia Gomez-Escobar1,*, Nasser Almobadel1,*, Othman Alzahrani1,*, Julia Feichtinger2,3,*, Vicente Planells-Palop1,*, Zafer Alshehri1, Gerhard G. Thallinger2,3, Jane A. Wakeman1 and Ramsay J. McFarlane1 1 North West Cancer Research Institute, School of Medical Sciences, Bangor University, Bangor, Gwynedd, United Kingdom 2 Computational Biotechnology and Bioinformatics Group, Institute of Molecular Biotechnology, Graz University of Technology, Graz, Austria 3 Omics Center Graz, BioTechMed Graz, Graz, Austria * These authors have contributed equally to this work Correspondence to: Ramsay J. McFarlane, email: [email protected] Keywords: telomeres, Translin, Trax, C3PO, TERRA, Chromosome Section Received: February 15, 2016 Accepted: April 19, 2016 Published: May 10, 2016 ABSTRACT Translin and Trax proteins are highly conserved nucleic acid binding proteins that have been implicated in RNA regulation in a range of biological processes including tRNA processing, RNA interference, microRNA degradation during oncogenesis, spermatogenesis and neuronal regulation. Here, we explore the function of this paralogue pair of proteins in the fission yeast. Using transcript analysis we demonstrate a reciprocal mechanism for control of telomere-associated transcripts. Mutation of tfx1+ (Trax) elevates transcript levels from silenced sub-telomeric regions of the genome, but not other silenced regions, such as the peri-centromeric heterochromatin. In the case of some sub-telomeric transcripts, but not all, this elevation is dependent on the Trax paralogue, Tsn1 (Translin). In a reciprocal fashion, Tsn1 (Translin) serves to repress levels of transcripts (TERRAs) from the telomeric repeats, whereas Tfx1 serves to maintain these elevated levels.
    [Show full text]
  • Potential Impact of Mir-137 and Its Targets in Schizophrenia
    Georgia State University ScholarWorks @ Georgia State University Psychology Faculty Publications Department of Psychology 4-2013 Potential Impact of miR-137 and Its Targets in Schizophrenia Carrie Wright University of New Mexico, [email protected] Jessica Turner Georgia State University, [email protected] Vince D. Calhoun University of New Mexico, [email protected] Nora I. Perrone-Bizzozero University of New Mexico, [email protected] Follow this and additional works at: https://scholarworks.gsu.edu/psych_facpub Part of the Psychology Commons Recommended Citation Wright C, Turner JA, Calhoun VD and Perrone-Bizzozero N (2013) Potential impact of miR-137 and its tar- gets in schizophrenia. Front. Genet. 4:58. doi: http://dx.doi.org/10.3389/fgene.2013.00058 This Article is brought to you for free and open access by the Department of Psychology at ScholarWorks @ Georgia State University. It has been accepted for inclusion in Psychology Faculty Publications by an authorized administrator of ScholarWorks @ Georgia State University. For more information, please contact [email protected]. HYPOTHESIS AND THEORY ARTICLE published: 26 April 2013 doi: 10.3389/fgene.2013.00058 Potential impact of miR-137 and its targets in schizophrenia Carrie Wright 1, Jessica A.Turner 2,3*,Vince D. Calhoun2,3 and Nora Perrone-Bizzozero1* 1 Department of Neurosciences, Health Sciences Center, University of New Mexico, Albuquerque, NM, USA 2 The Mind Research Network, Albuquerque, NM, USA 3 Psychology Department, University of New Mexico, Albuquerque, NM, USA Edited by: The significant impact of microRNAs (miRNAs) on disease pathology is becoming increas- Francis J. McMahon, National ingly evident.These small non-coding RNAs have the ability to post-transcriptionally silence Institute of Mental Health, USA the expression of thousands of genes.
    [Show full text]
  • Alzahrani Phd 2018.Pdf
    Bangor University DOCTOR OF PHILOSOPHY Characterisation of novel genome regulation functions of the cancer-associated proteins Translin and Trax Alzahrani, Othman Award date: 2018 Awarding institution: Bangor University Link to publication General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal ? Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Download date: 04. Oct. 2021 Characterisation of novel genome regulation functions of the cancer- associated proteins Translin and Trax A thesis is submitted for the degree of Doctror of Philosophy at Bangor University By Othman Rashed Ahmed Alzahrani North West Cancer Research Fund Institute School of Biological Science University of Bangor United Kingdom December, 2017 Declaration and Consent Details of the Work I hereby agree to deposit the following item in the digital repository maintained by Bangor University and/or in any other repository authorized for use by Bangor University. Author Name: ………………………………………………………………………………………………….. Title: ………………………………………………………………………………………..………………………. Supervisor/Department: .................................................................................................................. Funding body (if any): ........................................................................................................................ Qualification/Degree obtained: ……………………………………………………………………….
    [Show full text]
  • Human Social Genomics in the Multi-Ethnic Study of Atherosclerosis
    Getting “Under the Skin”: Human Social Genomics in the Multi-Ethnic Study of Atherosclerosis by Kristen Monét Brown A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy (Epidemiological Science) in the University of Michigan 2017 Doctoral Committee: Professor Ana V. Diez-Roux, Co-Chair, Drexel University Professor Sharon R. Kardia, Co-Chair Professor Bhramar Mukherjee Assistant Professor Belinda Needham Assistant Professor Jennifer A. Smith © Kristen Monét Brown, 2017 [email protected] ORCID iD: 0000-0002-9955-0568 Dedication I dedicate this dissertation to my grandmother, Gertrude Delores Hampton. Nanny, no one wanted to see me become “Dr. Brown” more than you. I know that you are standing over the bannister of heaven smiling and beaming with pride. I love you more than my words could ever fully express. ii Acknowledgements First, I give honor to God, who is the head of my life. Truly, without Him, none of this would be possible. Countless times throughout this doctoral journey I have relied my favorite scripture, “And we know that all things work together for good, to them that love God, to them who are called according to His purpose (Romans 8:28).” Secondly, I acknowledge my parents, James and Marilyn Brown. From an early age, you two instilled in me the value of education and have been my biggest cheerleaders throughout my entire life. I thank you for your unconditional love, encouragement, sacrifices, and support. I would not be here today without you. I truly thank God that out of the all of the people in the world that He could have chosen to be my parents, that He chose the two of you.
    [Show full text]
  • Low-Resolution Structure of Drosophila Translin ⇑ Vinay Kumar , Gagan D
    FEBS Open Bio 2 (2012) 37–46 journal homepage: www.elsevier.com/locate/febsopenbio Low-resolution structure of Drosophila translin ⇑ Vinay Kumar , Gagan D. Gupta High Pressure & Synchrotron Radiation Physics Division, Bhabha Atomic Research Centre, Mumbai 400085, India article info abstract Article history: Crystals of native Drosophila melanogaster translin diffracted to 7 Å resolution. Reductive methyla- Received 1 March 2012 tion of the protein improved crystal quality. The native and methylated proteins showed similar Revised 6 March 2012 profiles in size-exclusion chromatography analyses but the methylated protein displayed reduced Accepted 6 March 2012 DNA-binding activity. Crystals of the methylated protein diffracted to 4.2 Å resolution at BM14 of the ESRF synchrotron. Crystals with 49% solvent content belonged to monoclinic space group P21 with eight protomers in the asymmetric unit. Only 2% of low-resolution structures with similar low percentage solvent content were found in the PDB. The crystal structure, solved by molecular Keywords: replacement method, refined to R (R ) of 0.24 (0.29) with excellent stereochemistry. The crys- Crystal structure work free Oligomeric status tal structure clearly shows that drosophila protein exists as an octamer, and not as a decamer as Low-resolution structure refinement expected from gel-filtration elution profiles. The similar octameric quaternary fold in translin Reductive methylation orthologs and in translin–TRAX complexes suggests an up-down dimer as the basic structural sub- Drosophila melanogaster translin unit of translin-like proteins. The drosophila oligomer displays asymmetric assembly and increased radius of gyration that accounts for the observed differences between the elution profiles of human and drosophila proteins on gel-filtration columns.
    [Show full text]
  • Crystal Structure of TB-RBP, a Novel RNA-Binding and Regulating Protein
    B doi:10.1016/S0022-2836(02)00364-9 available online at http://www.idealibrary.com on w J. Mol. Biol. (2002) 319, 1049–1057 Crystal Structure of TB-RBP, a Novel RNA-binding and Regulating Protein John M. Pascal1, P. John Hart2, Norman B. Hecht3 and Jon D. Robertus1* 1Institute for Cellular and The testis/brain-RNA-binding protein (TB-RBP) spatially and temporally Molecular Biology controls the expression of specific mRNAs in developing male germ cells and the Department of and brain cells, and is implicated in DNA recombination and repair Chemistry and Biochemistry events. We report the 2.65 A˚ crystal structure of mouse TB-RBP. The University of Texas at Austin structure is predominantly a-helical and exhibits a novel protein fold Austin, TX 78712, USA and mode of assembly. Crystal symmetry and molecular symmetry com- bine to form an octet of TB-RBP monomers in the shape of an elongated 2Department of Biochemistry spherical particle with a large cavity at its center. Amino acid residues University of Texas Health that affect RNA and DNA binding are located on the interior surface of Science Center at San Antonio the assembled particle, and a putative nucleotide-binding domain that San Antonio, TX 78229, USA controls RNA binding is located at a dimer interface. Other modes of 3Center for Research on assembly are suggested for TB-RBP based on our structure and recently Reproduction and Women’s reported electron microscopic reconstructions of human TB-RBP. Health and Department of q 2002 Elsevier Science Ltd. All rights reserved Obstetrics and Gynecology University of Pennsylvania School of Medicine Philadelphia, PA 19104, USA Keywords: X-ray structure; novel fold; RNA-binding protein; mRNA *Corresponding author expression control Introduction Testis/brain-RNA-binding protein (TB-RBP) was identified initially as a protein able to suppress the Mammalian spermatogenesis proceeds in stages 1 translation of stored mRNAs that contained that require various forms of gene expression.
    [Show full text]
  • Genetic Inactivation of the Translin/Trax Microrna-Degrading Enzyme Phenocopies the Robust Adiposity Induced by Translin (Tsn) Deletion
    bioRxiv preprint doi: https://doi.org/10.1101/2020.04.25.060665; this version posted April 25, 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. Genetic inactivation of the translin/trax microRNA-degrading enzyme phenocopies the robust adiposity induced by Translin (Tsn) deletion Xiuping Fu, Aparna P. Shah, Zhi Li, Mengni Li2, Kellie L. Tamashiro, Jay M. Baraban 1The Solomon H. Snyder Department of Neuroscience and 2Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21205 Author email addresses: Xiuping Fu: [email protected] Aparna P. Shah: [email protected] Zhi Li: [email protected] Mengni Li: [email protected] Kellie L. Tamashiro: [email protected] Jay M. Baraban: [email protected] Corresponding author: Jay M. Baraban, MD, PhD 725 N. Wolfe Street Baltimore, MD 21205 phone: 410-955-2499 bioRxiv preprint doi: https://doi.org/10.1101/2020.04.25.060665; this version posted April 25, 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. Abstract Objective: Deletion of Translin (Tsn) from mice induces an unusual metabolic profile characterized by robust adiposity, normal body weight and glucose tolerance. Translin (TN) protein and its partner, trax (TX), form the TN/TX microRNA-degrading enzyme.
    [Show full text]
  • Autocrine IFN Signaling Inducing Profibrotic Fibroblast Responses By
    Downloaded from http://www.jimmunol.org/ by guest on September 23, 2021 Inducing is online at: average * The Journal of Immunology , 11 of which you can access for free at: 2013; 191:2956-2966; Prepublished online 16 from submission to initial decision 4 weeks from acceptance to publication August 2013; doi: 10.4049/jimmunol.1300376 http://www.jimmunol.org/content/191/6/2956 A Synthetic TLR3 Ligand Mitigates Profibrotic Fibroblast Responses by Autocrine IFN Signaling Feng Fang, Kohtaro Ooka, Xiaoyong Sun, Ruchi Shah, Swati Bhattacharyya, Jun Wei and John Varga J Immunol cites 49 articles Submit online. Every submission reviewed by practicing scientists ? is published twice each month by Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts http://jimmunol.org/subscription Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html http://www.jimmunol.org/content/suppl/2013/08/20/jimmunol.130037 6.DC1 This article http://www.jimmunol.org/content/191/6/2956.full#ref-list-1 Information about subscribing to The JI No Triage! Fast Publication! Rapid Reviews! 30 days* Why • • • Material References Permissions Email Alerts Subscription Supplementary The Journal of Immunology The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2013 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. This information is current as of September 23, 2021. The Journal of Immunology A Synthetic TLR3 Ligand Mitigates Profibrotic Fibroblast Responses by Inducing Autocrine IFN Signaling Feng Fang,* Kohtaro Ooka,* Xiaoyong Sun,† Ruchi Shah,* Swati Bhattacharyya,* Jun Wei,* and John Varga* Activation of TLR3 by exogenous microbial ligands or endogenous injury-associated ligands leads to production of type I IFN.
    [Show full text]
  • A Genomic View of Estrogen Actions in Human Breast Cancer Cells by Expression Profiling of the Hormone-Responsive Transcriptome
    719 A genomic view of estrogen actions in human breast cancer cells by expression profiling of the hormone-responsive transcriptome Luigi Cicatiello1, Claudio Scafoglio1, Lucia Altucci1, Massimo Cancemi1, Guido Natoli1, Angelo Facchiano2, Giovanni Iazzetti3, Raffaele Calogero4, Nicoletta Biglia6, Michele De Bortoli5,7, Christian Sfiligoi7, Piero Sismondi6,7, Francesco Bresciani1 and Alessandro Weisz1 1Dipartimento di Patologia generale, Seconda Università degli Studi di Napoli, Vico L. De Crecchio 7, 80138 Napoli, Italy 2Istituto di Scienze dell’Alimentazione del Consiglio Nazionale delle Ricerche, Avellino, Italy 3Dipartimento di Genetica, Biologia generale e molecolare, Università di Napoli ‘Federico II’, Napoli, Italy 4Dipartimento di Scienze cliniche e biologiche, Università degli Studi di Torino, Torino, Italy 5Dipartimento di Scienze oncologiche, Università degli Studi di Torino, Torino, Italy 6Dipartimento di Discipline ostetriche e ginecologiche, Università degli Studi di Torino, Torino, Italy 7Laboratorio di Ginecologia oncologica, Istituto per la Ricerca e la Cura del Cancro, Candiolo, Italy (Requests for offprints should be addressed to A Weisz; Email: [email protected]) Abstract Estrogen controls key cellular functions of responsive cells including the ability to survive, replicate, communicate and adapt to the extracellular milieu. Changes in the expression of 8400 genes were monitored here by cDNA microarray analysis during the first 32 h of human breast cancer (BC) ZR-75·1 cell stimulation with a mitogenic dose of 17-estradiol, a timing which corresponds to completion of a full mitotic cycle in hormone-stimulated cells. Hierarchical clustering of 344 genes whose expression either increases or decreases significantly in response to estrogen reveals that the gene expression program activated by the hormone in these cells shows 8 main patterns of gene activation/inhibition.
    [Show full text]
  • Genome-Wide Association Studies for Sperm Traits in Assaf Sheep Breed
    ANIMAL-100065; No of Pages 9 Animal xxx (2021) xxx Contents lists available at ScienceDirect Animal The international journal of animal biosciences Genome-wide association studies for sperm traits in Assaf sheep breed M. Serrano a,⁎, M. Ramón b, J.H. Calvo c,f, M.Á. Jiménez a, F. Freire d, J.M. Vázquez d, J.J. Arranz e a Departamento de Mejora Genética Animal, INIA, 28040 Madrid, Spain b IRIAF-CERSYRA, Valdepeñas 13300, Ciudad Real, Spain c Unidad de Tecnología en Producción Animal, CITA, 59059 Zaragoza, Spain d OVIGEN, Granja Florencia s/n, Ctra. Villalazán-Peleagonzalo, 49800 Toro, Zamora, Spain e Departamento de Producción Animal, Universidad de León, 24007 León, Spain f ARAID, 50004 Zaragoza, Spain article info abstract Article history: Sperm quality traits routinely collected by artificial insemination (AI) center for rams progeny test are related Received 6 May 2020 with the capacity to produce sperm doses for AI and, in more or less grade, with males' fertility. Low-quality ejac- Received in revised form 20 August 2020 ulates are unuseful to perform AI sperm doses, which suppose high economic loses for the AI center. Moreover, Accepted 21 August 2020 sperm quality traits have low heritability values which make traditional genetic selection little efficient to its im- Available online xxxx provement. In this work, a genome-wide association study (GWAS) was conducted by using sperm quality traits data and 50 K Affymetrix custom chip genotypes of 429 rams of Assaf breed from OVIGEN AI centre. Furthermore, Keywords: Association study 47 of these rams were also genotyped with the Illumina HD Ovine BeadChip, and therefore HD genotypes were Pseudo-phenotypes imputed for all rams with phenotype data.
    [Show full text]