DOCSLIB.ORG

Retroposition As a Source of Antisense Long Non-Coding Rnas with Possible Regulatory Functions

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Retroposition As a Source of Antisense Long Non-Coding Rnas with Possible Regulatory Functions Vol. 63, No 4/2016 825–833 https://doi.org/10.18388/abp.2016_1354 Regular paper Retroposition as a source of antisense long non-coding RNAs with possible regulatory functions# Oleksii Bryzghalov*, Michał Wojciech Szcześniak** and Izabela Makałowska Department of Integrative Genomics, Institute of Antropology, Adam Mickiewicz University in Poznan, Poznań, Poland# Long non-coding RNAs (lncRNAs) are a class of intensely possible that a large portion of lncRNAs has no bio- studied, yet enigmatic molecules that make up a sub- logical role and represent a mere transcriptional noise or stantial portion of the human transcriptome. In this that the act of their transcription itself has a biological work, we link the origins and functions of some lncRNAs meaning, rather than their sequence does (Kornienko et to retroposition, a process resulting in the creation of al., 2013). Regarding the modes of action, a number of intronless copies (retrocopies) of the so-called parental scenarios has been proposed, with transcriptional regula- genes. We found 35 human retrocopies transcribed in tion being the best studied and being achieved through antisense and giving rise to 58 lncRNA transcripts. These several mechanisms, such as promoter modifications, lncRNAs share sequence similarity with the correspond- creating a permissive chromatin environment or bind- ing parental genes but in the sense/antisense orienta- ing transport factors to inhibit the nuclear localization of tion, meaning they have the potential to interact with specific transcription factors (Kugel & Goodrich, 2012). each other and to form RNA:RNA duplexes. We took a In contrast to transcription-related mechanisms, little is closer look at these duplexes and found that 10 of the known about the roles lncRNAs play upon base-pairing lncRNAs might regulate parental gene expression and with fully or partially complementary mate mRNAs. In processing at the pre-mRNA and mRNA levels. Further that scenario, lncRNAs could affect the stability, pro- analysis of the co-expression and expression correlation cessing and expression levels of other transcripts (Geisler provided support for the existence of functional cou- & Coller, 2013). One possibility is modulating the pre- pling between lncRNAs and their mate parental gene mRNA splicing by splice site masking and subsequent transcripts. blocking of the spliceosome assembly, which requires an extensive complementarity with a regulated pre-mR- Key words: lncRNAs, long non-coding RNAs, retroposition, retrocop- NA molecule. Such complementarity occurs by defini- ies, antisense transcription, RNA:RNA duplexes tion between the natural cis antisense transcripts (cis- Received: 04 June, 2016; revised: 30 June, 2016; accepted: 19 July, NATs), but interactions in trans are also possible. Several 2016; available on-line: 02 November, 2016 lncRNAs are known to be involved in this type of regu- lation. For instance, it was shown that NATs influence the splicing patterns of mRNAs at the neuroblastoma INTRODUCTION MYC, c-ErbAalpha and ZEB2 loci in mammals (Beltran et al., 2008). In the case of neuroblastoma MYC and c- In higher eukaryotes, non-coding RNAs, such as ErbAalpha, this was suggested to be achieved through miRNAs (microRNAs) and lncRNAs (long non-coding formation of RNA:RNA duplexes, which then inhibit RNAs), represent considerable portions of the transcrip- splicing. At the ZEB2 locus, lncRNA expression inhibits tome, with the latter class represented by 28 031 tran- splicing of an intron that contains an internal ribosome scripts in humans (Ensembl 83), compared to 79 930 entry site (IRES). Translation of ZEB2 relies on this protein-coding transcripts. Some other sources provide IRES; therefore, expression of the NAT indirectly facili- even higher numbers of these RNAs, such as NON- tates expression of ZEB2 protein. In addition to splic- CODE (Zhao et al., 2016), with 141 353 lncRNAs. This ing modulation, other regulatory mechanisms triggered abundance of lncRNAs sparked interest in deciphering by lncRNA:RNA duplexes are possible in humans, and their functions, origins and evolution. However, the they include adenine to inosine RNA editing at dsRNA tasks appear to be even more demanding than in the regions, mRNA stability control by abrogation of miR- case of protein-coding genes, and as a result, the vast NA-induced repression and guiding protein-coding genes majority of lncRNAs has no biological role assigned. to degradation within a Staufen-mediated decay (SMD) In particular, due to poor evolutionary conservation of pathway (Geisler & Coller, 2013). Recently, the potential their sequences, homology-based functional assignment * can be applied to only a small subset of lncRNAs. Ad- e-mail: [email protected] *These authors contributed equally to this work ditionally, detailed studies of the selected lncRNAs, such #Information about a preliminary report on the same subject pre- as HOTAIR (Tsai et al., 2010), ANRIL (Yap et al., 2010), sented at scientific meetings:Oleksii Bryzghalov, Michał Szcześniak, and ZEB2-NAT (Beltran et al., 2008), indicate a high Izabela Makałowska. Polish Evolutionary Conference 2015, Poznan, heterogeneity of their modes of action, making the in Poland. Potential roles of retroposition-derived lncRNAs in splicing regulation (poster); book of abstracts, page 36. silico functional studies quite inaccurate. The accumulated #Formely: Department of Bioinformatics, Institute of Molecular Biolo- data associate lncRNAs with biological processes such gy and Biotechnology, Adam Mickiewicz University in Poznan, Poland. as transcription, splicing, translation, protein localization, Abbreviations: lncRNAs, long non-coding RNAs; miRNAs, micro- cell cycle and apoptosis. They have also been linked to RNAs; NATs, natural antisense transcripts; IRES, internal ribosome entry site; SMD, Staufen-mediated decay; hnRNPs, heterogeneous a number of human diseases, including cancers. It is nuclear ribonucleoproteins; asRNAs, antisense RNAs 826 O. Bryzghalov and others 2016 of lncRNAs to exert regulatory roles through RNA:RNA ies that could not be mapped to Ensembl or failed co- base-pairings has been assessed for the human transcrip- ordinates transformation were eliminated from further tome (Szczesniak and Makałowska, 2016) and for several steps. As a result, the original set of 4 927 human ret- model plant species (Szczesniak et al., 2016). rocopies from the RetrogeneDB was reduced to 4 675 In this work, we scanned the human lncRNAs to loci (Fig. 2). For gene expression analysis, pre-calculated identify those transcribed in antisense to retroposition- expression estimates from 153 stranded RNA-Seq librar- derived copies (retrocopies) of protein-coding genes. ies (Suppl. Table 2 at www.actabp.pl) were downloaded In retroposition, an mRNA molecule is reversely tran- from ENCODE (ENCODE Project Consortium 2012). scribed into cDNA, which occasionally becomes inserted Ab initio transcriptome assembly for chimp. Pan into the genome at a random location (Fig. 1A). The troglodytes genome and annotation data in the GTF for- resulting new copy (retrocopy) of the so-called parental mat were downloaded from Ensembl 83 (Herrero et al., gene typically is not functional because it lacks the core 2016). Nineteen stranded RNA-Seq libraries were down- promoter and other regulatory sequences that would en- loaded from the Sequence Read Archive database (Ko- able its transcription. In some cases, however, retrocop- dama et al., 2012) in the FASTQ format (Suppl. Table 3 ies use upstream promoters, either new ones (exaptation at www.actabp.pl). The reads were filtered for quality, of cryptic promoter sequences) or the ones from oth- and adapters were trimmed using Trimmomatic (Bolger er genes; such new genes, called retrogenes, constitute et al., 2014). For quality filtering, the following param- ca. 7.4% of the human gene set. They might evolve eters were used: LEADING: 20, TRAILING: 20, SLID- functions other than those of parental genes (neofunc- INGWINDOW: 5:20, and MINLEN: 50. Additionally, tionalization), play the same roles but with different spa- reads mapping to rRNA sequences were discarded using tio-temporal pattern (subfunctionalization) or replace the Bowtie 2 (Langmead & Salzberg, 2012). The processed parental gene (orphan retrogenes) (Ciomborowska et al., paired-end reads were then mapped to the chimp ge- 2013). Finally, some of them are transcribed from the an- nome with HISAT (Kim et al., 2015) using the following tisense strand, resulting in production of long non-cod- settings: -X 1000, --rna-strandness RF, and --phred33, in ing RNAs, as shown in this study. These lncRNAs are addition to the splice site data from Ensembl. The re- expected to have functions other than the corresponding sulting SAM file was then converted to the BAM for- retrocopies or parental genes due to the lack of sequence mat and sorted with SAMtools (Li et al., 2009). Finally, similarity in the sense/sense orientation. A key to under- StringTie (Pertea et al., 2015) was used to assemble the standing their functions might be the observation that as transcriptome using known annotations in the GTF a consequence of their origin, these lncRNAs are fully or format as a reference. The procedure was repeated for partially complementary to their parental genes and are each sequencing library, resulting in 19 GTF files. The thus able to interact with each other at the RNA level. files were then merged with Cuffmerge from the Cuf- Keeping this in mind, we performed in silico
Load more

Recommended publications
  • The Endocytic Membrane Trafficking Pathway Plays a Major Role
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by University of Liverpool Repository RESEARCH ARTICLE The Endocytic Membrane Trafficking Pathway Plays a Major Role in the Risk of Parkinson’s Disease Sara Bandres-Ciga, PhD,1,2 Sara Saez-Atienzar, PhD,3 Luis Bonet-Ponce, PhD,4 Kimberley Billingsley, MSc,1,5,6 Dan Vitale, MSc,7 Cornelis Blauwendraat, PhD,1 Jesse Raphael Gibbs, PhD,7 Lasse Pihlstrøm, MD, PhD,8 Ziv Gan-Or, MD, PhD,9,10 The International Parkinson’s Disease Genomics Consortium (IPDGC), Mark R. Cookson, PhD,4 Mike A. Nalls, PhD,1,11 and Andrew B. Singleton, PhD1* 1Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA 2Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), Granada, Spain 3Transgenics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA 4Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA 5Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom 6Department of Pathophysiology, University of Tartu, Tartu, Estonia 7Computational Biology Group, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA 8Department of Neurology, Oslo University Hospital, Oslo, Norway 9Department of Neurology and Neurosurgery, Department of Human Genetics, McGill University, Montréal, Quebec, Canada 10Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada 11Data Tecnica International, Glen Echo, Maryland, USA ABSTRACT studies, summary-data based Mendelian randomization Background: PD is a complex polygenic disorder.
    [Show full text]
  • The Function and Mechanism of Chmp1a in Tumor Development
    Marshall University Marshall Digital Scholar Theses, Dissertations and Capstones 1-1-2008 The uncF tion and Mechanism of Chmp1A in Tumor Development Jing Li [email protected] Follow this and additional works at: http://mds.marshall.edu/etd Part of the Biological Phenomena, Cell Phenomena, and Immunity Commons, and the Oncology Commons Recommended Citation Li, Jing, "The unctF ion and Mechanism of Chmp1A in Tumor Development" (2008). Theses, Dissertations and Capstones. Paper 120. This Thesis is brought to you for free and open access by Marshall Digital Scholar. It has been accepted for inclusion in Theses, Dissertations and Capstones by an authorized administrator of Marshall Digital Scholar. For more information, please contact [email protected]. THE FUNCTION AND MECHANISM OF CHMP1A IN TUMOR DEVELOPMENT Thesis submitted to the Graduate College of Marshall University In partial fulfillment of the requirements for the degree of Master of Science in Biological Sciences by Jing Li Committee Members: Dr. Simon Collier, Committee Chairperson Dr. Maiyon Park Dr. Guozhang Zhu Marshall University May 2008 ABSTRACT THE FUNCTION AND MECHANISM OF CHMP1A IN TUMOR DEVELOPMENT By Jing Li Chmp1A (Chromatin modifying protein 1A/Charged multivesicular protein 1A) is a member of the ESCRT-III (Endosomal Sorting Complex Required for Transport) family. ESCRT complexes play central roles in endosome mediated trafficking via MVB (multivesicular body) formation and sorting. Chmp1A is a potential tumor suppressor, especially in the pancreas. Knockdown of Chmp1A resulted in an increase of anchorage-independent growth of HEK 293T cells. Chmp1A shRNA expressing HEK 293T cells transformed these non-tumorigeneic cells to form tumors in xenograft assays.
    [Show full text]
  • Supp Material.Pdf
    Simon et al. Supplementary information: Table of contents p.1 Supplementary material and methods p.2-4 • PoIy(I)-poly(C) Treatment • Flow Cytometry and Immunohistochemistry • Western Blotting • Quantitative RT-PCR • Fluorescence In Situ Hybridization • RNA-Seq • Exome capture • Sequencing Supplementary Figures and Tables Suppl. items Description pages Figure 1 Inactivation of Ezh2 affects normal thymocyte development 5 Figure 2 Ezh2 mouse leukemias express cell surface T cell receptor 6 Figure 3 Expression of EZH2 and Hox genes in T-ALL 7 Figure 4 Additional mutation et deletion of chromatin modifiers in T-ALL 8 Figure 5 PRC2 expression and activity in human lymphoproliferative disease 9 Figure 6 PRC2 regulatory network (String analysis) 10 Table 1 Primers and probes for detection of PRC2 genes 11 Table 2 Patient and T-ALL characteristics 12 Table 3 Statistics of RNA and DNA sequencing 13 Table 4 Mutations found in human T-ALLs (see Fig. 3D and Suppl. Fig. 4) 14 Table 5 SNP populations in analyzed human T-ALL samples 15 Table 6 List of altered genes in T-ALL for DAVID analysis 20 Table 7 List of David functional clusters 31 Table 8 List of acquired SNP tested in normal non leukemic DNA 32 1 Simon et al. Supplementary Material and Methods PoIy(I)-poly(C) Treatment. pIpC (GE Healthcare Lifesciences) was dissolved in endotoxin-free D-PBS (Gibco) at a concentration of 2 mg/ml. Mice received four consecutive injections of 150 μg pIpC every other day. The day of the last pIpC injection was designated as day 0 of experiment.
    [Show full text]
  • Identification and Characterization of Genes Essential for Human Brain Development
    Identification and Characterization of Genes Essential for Human Brain Development The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Ganesh, Vijay S. 2012. Identification and Characterization of Genes Essential for Human Brain Development. Doctoral dissertation, Harvard University. Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:9773743 Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#LAA Copyright © 2012 by Vijay S. Ganesh All rights reserved. Dissertation Advisor: Dr. Christopher A. Walsh Author: Vijay S. Ganesh Identification and Characterization of Genes Essential for Human Brain Development Abstract The human brain is a network of ninety billion neurons that allows for many of the behavioral adaptations considered unique to our species. One-fifth of these neurons are layered in an epithelial sheet known as the cerebral cortex, which is exquisitely folded into convolutions called gyri. Defects in neuronal number clinically present with microcephaly (Greek for “small head”), and in inherited cases these defects can be linked to mutations that identify genes essential for neural progenitor proliferation. Most microcephaly genes are characterized to play a role in the centrosome, however rarer presentations of microcephaly have identified different mechanisms. Charged multivesicular body protein/Chromatin modifying protein 1A (CHMP1A) is a member of the ESCRT-III endosomal sorting complex, but is also suggested to localize to the nuclear matrix and regulate chromatin.
    [Show full text]
  • CHMP5 Mouse Monoclonal Antibody [Clone ID: OTI5C7] Product Data
    OriGene Technologies, Inc. 9620 Medical Center Drive, Ste 200 Rockville, MD 20850, US Phone: +1-888-267-4436 [email protected] EU: [email protected] CN: [email protected] Product datasheet for TA808523 CHMP5 Mouse Monoclonal Antibody [Clone ID: OTI5C7] Product data: Product Type: Primary Antibodies Clone Name: OTI5C7 Applications: IHC, WB Recommended Dilution: WB 1:2000, IHC 1:150 Reactivity: Human, Mouse, Rat Host: Mouse Isotype: IgG1 Clonality: Monoclonal Immunogen: Full length human recombinant protein of human CHMP5 (NP_057494) produced in E.coli. Formulation: PBS (PH 7.3) containing 1% BSA, 50% glycerol and 0.02% sodium azide. Concentration: 1 mg/ml Purification: Purified from mouse ascites fluids or tissue culture supernatant by affinity chromatography (protein A/G) Conjugation: Unconjugated Storage: Store at -20°C as received. Stability: Stable for 12 months from date of receipt. Predicted Protein Size: 24.4 kDa Gene Name: charged multivesicular body protein 5 Database Link: NP_057494 Entrez Gene 76959 MouseEntrez Gene 297995 RatEntrez Gene 51510 Human Q9NZZ3 Background: CHMP5 belongs to the chromatin-modifying protein/charged multivesicular body protein (CHMP) family. These proteins are components of ESCRT-III (endosomal sorting complex required for transport III), a complex involved in degradation of surface receptor proteins and formation of endocytic multivesicular bodies (MVBs). Some CHMPs have both nuclear and cytoplasmic/vesicular distributions, and one such CHMP, CHMP1A (MIM 164010), is required for both MVB formation and regulation of cell cycle progression (Tsang et al., 2006 [PubMed 16730941]). [supplied by OMIM, Mar This product is to be used for laboratory only. Not for diagnostic or therapeutic use.
    [Show full text]
  • Chromosomal Microarray Analysis in Turkish Patients with Unexplained Developmental Delay and Intellectual Developmental Disorders
    177 Arch Neuropsychitry 2020;57:177−191 RESEARCH ARTICLE https://doi.org/10.29399/npa.24890 Chromosomal Microarray Analysis in Turkish Patients with Unexplained Developmental Delay and Intellectual Developmental Disorders Hakan GÜRKAN1 , Emine İkbal ATLI1 , Engin ATLI1 , Leyla BOZATLI2 , Mengühan ARAZ ALTAY2 , Sinem YALÇINTEPE1 , Yasemin ÖZEN1 , Damla EKER1 , Çisem AKURUT1 , Selma DEMİR1 , Işık GÖRKER2 1Faculty of Medicine, Department of Medical Genetics, Edirne, Trakya University, Edirne, Turkey 2Faculty of Medicine, Department of Child and Adolescent Psychiatry, Trakya University, Edirne, Turkey ABSTRACT Introduction: Aneuploids, copy number variations (CNVs), and single in 39 (39/123=31.7%) patients. Twelve CNV variant of unknown nucleotide variants in specific genes are the main genetic causes of significance (VUS) (9.75%) patients and 7 CNV benign (5.69%) patients developmental delay (DD) and intellectual disability disorder (IDD). were reported. In 6 patients, one or more pathogenic CNVs were These genetic changes can be detected using chromosome analysis, determined. Therefore, the diagnostic efficiency of CMA was found to chromosomal microarray (CMA), and next-generation DNA sequencing be 31.7% (39/123). techniques. Therefore; In this study, we aimed to investigate the Conclusion: Today, genetic analysis is still not part of the routine in the importance of CMA in determining the genomic etiology of unexplained evaluation of IDD patients who present to psychiatry clinics. A genetic DD and IDD in 123 patients. diagnosis from CMA can eliminate genetic question marks and thus Method: For 123 patients, chromosome analysis, DNA fragment analysis alter the clinical management of patients. Approximately one-third and microarray were performed. Conventional G-band karyotype of the positive CMA findings are clinically intervenable.
    [Show full text]
  • CHMP1A Encodes an Essential Regulator of BMI1-INK4A in Cerebellar Development
    CHMP1A encodes an essential regulator of BMI1-INK4A in cerebellar development The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters. Citation Mochida, Ganeshwaran H., Vijay S. Ganesh, Maria I. de Michelena, Hugo Dias, Kutay D. Atabay, Katie L. Kathrein, Emily Huang, et al. 2013. CHMP1A encodes an essential regulator of BMI1-INK4A in cerebellar development. Nature genetics 44(11): 1260-1264. Published Version doi:10.1038/ng.2425 Accessed February 19, 2015 12:08:00 PM EST Citable Link http://nrs.harvard.edu/urn-3:HUL.InstRepos:11181050 Terms of Use This article was downloaded from Harvard University's DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#LAA (Article begins on next page) NIH Public Access Author Manuscript Nat Genet. Author manuscript; available in PMC 2013 May 01. NIH-PA Author ManuscriptPublished NIH-PA Author Manuscript in final edited NIH-PA Author Manuscript form as: Nat Genet. 2012 November ; 44(11): 1260–1264. doi:10.1038/ng.2425. CHMP1A encodes an essential regulator of BMI1-INK4A in cerebellar development Ganeshwaran H. Mochida1,2,3,4,5,*, Vijay S. Ganesh1,2,3,6,*, Maria I. de Michelena7, Hugo Dias8, Kutay D. Atabay1,2,3, Katie L. Kathrein3,9,10,11, Emily Huang3,9,10,11, R. Sean Hill1,2,3, Jillian M. Felie1,2,3, Daniel Rakiec1,2,3, Danielle Gleason1,2,3, Anthony D. Hill12, Athar N.
    [Show full text]
  • HHS Public Access Author Manuscript
    HHS Public Access Author manuscript Author Manuscript Author ManuscriptNat Genet Author Manuscript. Author manuscript; Author Manuscript available in PMC 2013 May 01. Published in final edited form as: Nat Genet. 2012 November ; 44(11): 1260–1264. doi:10.1038/ng.2425. CHMP1A encodes an essential regulator of BMI1-INK4A in cerebellar development Ganeshwaran H. Mochida1,2,3,4,5,*, Vijay S. Ganesh1,2,3,6,*, Maria I. de Michelena7, Hugo Dias8, Kutay D. Atabay1,2,3, Katie L. Kathrein3,9,10,11, Emily Huang3,9,10,11, R. Sean Hill1,2,3, Jillian M. Felie1,2,3, Daniel Rakiec1,2,3, Danielle Gleason1,2,3, Anthony D. Hill12, Athar N. Malik6, Brenda J. Barry1,2,3, Jennifer N. Partlow1,2,3, Wen-Hann Tan1,4, Laurie J. Glader4,13, A. James Barkovich14, William B. Dobyns15, Leonard I. Zon3,4,9,10,11, and Christopher A. Walsh1,2,3,4,16 1Division of Genetics, Department of Medicine, Boston Children’s Hospital, Boston, MA, USA 2Manton Center for Orphan Disease Research, Boston Children’s Hospital, Boston, MA, USA 3Howard Hughes Medical Institute, Boston Children’s Hospital, Boston, MA, USA 4Departments of Pediatrics, Harvard Medical School, Boston, MA, USA Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms Corresponding author: Dr. Christopher A. Walsh, Division of Genetics, Boston Children’s Hospital, 300 Longwood Ave, CLS 15062.2, Boston, MA 02115, [email protected], Phone: 617-919-2923, Fax: 617-919-2010.
    [Show full text]
  • A Single Genetic Locus Controls Both Expression of DPEP1/CHMP1A and Kidney Disease Development Via Ferroptosis
    ARTICLE https://doi.org/10.1038/s41467-021-25377-x OPEN A single genetic locus controls both expression of DPEP1/CHMP1A and kidney disease development via ferroptosis Yuting Guan 1,2,9, Xiujie Liang1,2,9, Ziyuan Ma 1,2, Hailong Hu1,2, Hongbo Liu 1,2, Zhen Miao 1,2,3, ✉ Andreas Linkermann 4,5, Jacklyn N. Hellwege 6, Benjamin F. Voight 2,7,8 & Katalin Susztak 1,2 fi 1234567890():,; Genome-wide association studies (GWAS) have identi ed loci for kidney disease, but the causal variants, genes, and pathways remain unknown. Here we identify two kidney disease genes Dipeptidase 1 (DPEP1) and Charged Multivesicular Body Protein 1 A (CHMP1A) via the triangulation of kidney function GWAS, human kidney expression, and methylation quanti- tative trait loci. Using single-cell chromatin accessibility and genome editing, we fine map the region that controls the expression of both genes. Mouse genetic models demonstrate the causal roles of both genes in kidney disease. Cellular studies indicate that both Dpep1 and Chmp1a are important regulators of a single pathway, ferroptosis and lead to kidney disease development via altering cellular iron trafficking. 1 Department of Medicine, Renal Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. 2 Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. 3 Graduate group in Genomics and Computational Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. 4 Division of Nephrology, Department of Internal Medicine, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany.
    [Show full text]
  • Agricultural University of Athens
    ΓΕΩΠΟΝΙΚΟ ΠΑΝΕΠΙΣΤΗΜΙΟ ΑΘΗΝΩΝ ΣΧΟΛΗ ΕΠΙΣΤΗΜΩΝ ΤΩΝ ΖΩΩΝ ΤΜΗΜΑ ΕΠΙΣΤΗΜΗΣ ΖΩΙΚΗΣ ΠΑΡΑΓΩΓΗΣ ΕΡΓΑΣΤΗΡΙΟ ΓΕΝΙΚΗΣ ΚΑΙ ΕΙΔΙΚΗΣ ΖΩΟΤΕΧΝΙΑΣ ΔΙΔΑΚΤΟΡΙΚΗ ΔΙΑΤΡΙΒΗ Εντοπισμός γονιδιωματικών περιοχών και δικτύων γονιδίων που επηρεάζουν παραγωγικές και αναπαραγωγικές ιδιότητες σε πληθυσμούς κρεοπαραγωγικών ορνιθίων ΕΙΡΗΝΗ Κ. ΤΑΡΣΑΝΗ ΕΠΙΒΛΕΠΩΝ ΚΑΘΗΓΗΤΗΣ: ΑΝΤΩΝΙΟΣ ΚΟΜΙΝΑΚΗΣ ΑΘΗΝΑ 2020 ΔΙΔΑΚΤΟΡΙΚΗ ΔΙΑΤΡΙΒΗ Εντοπισμός γονιδιωματικών περιοχών και δικτύων γονιδίων που επηρεάζουν παραγωγικές και αναπαραγωγικές ιδιότητες σε πληθυσμούς κρεοπαραγωγικών ορνιθίων Genome-wide association analysis and gene network analysis for (re)production traits in commercial broilers ΕΙΡΗΝΗ Κ. ΤΑΡΣΑΝΗ ΕΠΙΒΛΕΠΩΝ ΚΑΘΗΓΗΤΗΣ: ΑΝΤΩΝΙΟΣ ΚΟΜΙΝΑΚΗΣ Τριμελής Επιτροπή: Aντώνιος Κομινάκης (Αν. Καθ. ΓΠΑ) Ανδρέας Κράνης (Eρευν. B, Παν. Εδιμβούργου) Αριάδνη Χάγερ (Επ. Καθ. ΓΠΑ) Επταμελής εξεταστική επιτροπή: Aντώνιος Κομινάκης (Αν. Καθ. ΓΠΑ) Ανδρέας Κράνης (Eρευν. B, Παν. Εδιμβούργου) Αριάδνη Χάγερ (Επ. Καθ. ΓΠΑ) Πηνελόπη Μπεμπέλη (Καθ. ΓΠΑ) Δημήτριος Βλαχάκης (Επ. Καθ. ΓΠΑ) Ευάγγελος Ζωίδης (Επ.Καθ. ΓΠΑ) Γεώργιος Θεοδώρου (Επ.Καθ. ΓΠΑ) 2 Εντοπισμός γονιδιωματικών περιοχών και δικτύων γονιδίων που επηρεάζουν παραγωγικές και αναπαραγωγικές ιδιότητες σε πληθυσμούς κρεοπαραγωγικών ορνιθίων Περίληψη Σκοπός της παρούσας διδακτορικής διατριβής ήταν ο εντοπισμός γενετικών δεικτών και υποψηφίων γονιδίων που εμπλέκονται στο γενετικό έλεγχο δύο τυπικών πολυγονιδιακών ιδιοτήτων σε κρεοπαραγωγικά ορνίθια. Μία ιδιότητα σχετίζεται με την ανάπτυξη (σωματικό βάρος στις 35 ημέρες, ΣΒ) και η άλλη με την αναπαραγωγική
    [Show full text]
  • Anti-CHMP5 Antibody (ARG40721)
    Product datasheet [email protected] ARG40721 Package: 50 μg anti-CHMP5 antibody Store at: -20°C Summary Product Description Rabbit Polyclonal antibody recognizes CHMP5 Tested Reactivity Hu Tested Application WB Host Rabbit Clonality Polyclonal Isotype IgG Target Name CHMP5 Antigen Species Human Immunogen Recombinant protein corresponding to aa. 1-219 of Human CHMP5. Conjugation Un-conjugated Alternate Names hVps60; Charged multivesicular body protein 5; SNF7 domain-containing protein 2; HSPC177; CGI-34; Vps60; PNAS-2; Chromatin-modifying protein 5; Vacuolar protein sorting-associated protein 60; SNF7DC2; C9orf83 Application Instructions Application table Application Dilution WB 2 µg/ml Application Note * The dilutions indicate recommended starting dilutions and the optimal dilutions or concentrations should be determined by the scientist. Calculated Mw 25 kDa Observed Size 25 kDa Properties Form Liquid Purification Caprylic acid ammonium sulfate precipitation. Buffer 0.01M PBS (pH 7.4), 0.03% Proclin 300 and 50% Glycerol. Preservative 0.03% Proclin 300 Stabilizer 50% Glycerol Storage instruction For continuous use, store undiluted antibody at 2-8°C for up to a week. For long-term storage, aliquot and store at -20°C. Storage in frost free freezers is not recommended. Avoid repeated freeze/thaw cycles. Suggest spin the vial prior to opening. The antibody solution should be gently mixed before use. Note For laboratory research only, not for drug, diagnostic or other use. www.arigobio.com 1/2 Bioinformation Gene Symbol CHMP5 Gene Full Name charged multivesicular body protein 5 Background CHMP5 belongs to the chromatin-modifying protein/charged multivesicular body protein (CHMP) family. These proteins are components of ESCRT-III (endosomal sorting complex required for transport III), a complex involved in degradation of surface receptor proteins and formation of endocytic multivesicular bodies (MVBs).
    [Show full text]
  • The ESCRT-III Proteins IST1 and CHMP1B Assemble Around Nucleic Acids
    bioRxiv preprint doi: https://doi.org/10.1101/386532; this version posted August 7, 2018. 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. The ESCRT-III proteins IST1 and CHMP1B assemble around nucleic acids Nathaniel Talledge#1,2,3,4, John McCullough#1, Dawn Wenzel1, Henry C. Nguyen2,3, Matthew S. Lalonde1, Monika Bajorek1, Jack Skalicky1, Adam Frost1,2,3,4,*, Wesley I. Sundqust1,* 1 Department of Biochemistry, University of Utah, Salt Lake City, UT 84112, United States. 2 Department of Biochemistry & Biophysics, University of California, San Francisco, San Francisco, CA 94158, United States. 3 California Institute for Quantitative Biomedical Research, University of California, San Francisco, United States. 4 Chan Zuckerberg Biohub, United States. # These authors contributed equally *Co-corresponding authors 1 bioRxiv preprint doi: https://doi.org/10.1101/386532; this version posted August 7, 2018. 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 ESCRT-III proteins can promote inside-out or outside-in membrane tubulation and fission. In addition, several observations suggest that ESCRT factors may also associate with nucleic acids during development, different stages of the cell cycle, and during retro- transposition of parasitic nucleic acids like LINE1 elements.
    [Show full text]