Bone marrow failure and developmental delay caused by mutations in poly(A)-specific ribonuclease (PARN)

Journal of Medical Genetics
Santhosh DhanrajYigal Dror

Abstract

Deadenylation regulates RNA function and fate. Poly(A)-specific ribonuclease (PARN) is a deadenylase that processes mRNAs and non-coding RNA. Little is known about the biological significance of germline mutations in PARN. We identified mutations in PARN in patients with haematological and neurological manifestations. Genomic, biochemical and knockdown experiments in human marrow cells and in zebrafish have been performed to clarify the role of PARN in the human disease. We identified large monoallelic deletions in PARN in four patients with developmental delay or mental illness. One patient in particular had a severe neurological phenotype, central hypomyelination and bone marrow failure. This patient had an additional missense mutation on the non-deleted allele and severely reduced PARN protein and deadenylation activity. Cells from this patient had impaired oligoadenylation of specific H/ACA box small nucleolar RNAs. Importantly, PARN-deficient patient cells manifested short telomeres and an aberrant ribosome profile similar to those described in some variants of dyskeratosis congenita. Knocking down PARN in human marrow cells and zebrafish impaired haematopoiesis, providing further evidence for a causal link with the human ...Continue Reading

References

Oct 1, 1996·Molecular and Cellular Biology·C E BrownA B Sachs
Dec 16, 1998·Science·UNKNOWN C. elegans Sequencing Consortium
May 22, 2001·The Journal of Biological Chemistry·J MartînezA Virtanen
Dec 3, 2002·Science·Livio PellizzoniGideon Dreyfuss
Jul 9, 2004·Proceedings of the National Academy of Sciences of the United States of America·Yuko MochizukiPhilip J Mason
Apr 8, 2006·Human Molecular Genetics·Brian C KraemerGerard D Schellenberg
Feb 24, 2007·Nature Reviews. Molecular Cell Biology·A Gregory MateraMichael P Terns
Nov 15, 2008·Apoptosis : an International Journal on Programmed Cell Death·Ken-Ichiro WatanabeYigal Dror
Dec 30, 2008·Methods in Enzymology·Elizabeth L Murray, Daniel R Schoenberg
Feb 17, 2009·Structure·Mousheng WuHaiwei Song
Nov 11, 2009·The Journal of Biological Chemistry·Niklas HenrikssonAnders Virtanen
Oct 26, 2010·American Journal of Human Genetics·Andrew H CrosbyRobert N Lightowlers
Jan 20, 2011·Nature Reviews. Genetics·Andrea PauliAlexander F Schier
Feb 19, 2011·Blood·Niccolò BolliA Thomas Look
Jan 10, 2012·Current Opinion in Pediatrics·Shefali Parikh, Monica Bessler
Jul 28, 2012·Current Medicinal Chemistry·N A A BalatsosC Stathopoulos
Nov 2, 2012·Blood·Nicholas BurwickAkiko Shimamura
Jan 11, 2013·Pediatric Blood & Cancer·Santhosh DhanrajYigal Dror
Mar 19, 2013·Critical Reviews in Biochemistry and Molecular Biology·Anders VirtanenMikael Nissbeck
Jul 12, 2013·Journal of Cell Science·Marco NouschChristian R Eckmann
Nov 5, 2014·Wiley Interdisciplinary Reviews. RNA·Mary McMahonDavide Ruggero
Apr 22, 2015·The Journal of Clinical Investigation·Hemanth TummalaInderjeet Dokal

❮ Previous
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Citations

Jan 27, 2016·Pediatric Neurology·Ashley M BurrisSharon A Savage
Dec 3, 2015·Cell Reports·Chi-Kang TsengPeter Baumann
Mar 8, 2016·Nature Structural & Molecular Biology·Siddharth ShuklaRoy Parker
Jul 29, 2016·Molecular Genetics & Genomic Medicine·Shahinaz M GadallaSharon A Savage
Feb 26, 2016·Journal of Medical Genetics·Chao Xing, Christine Kim Garcia
Jun 7, 2016·Trends in Molecular Medicine·Siddharth Shukla, Roy Parker
Aug 3, 2016·The Journal of Clinical Investigation·Baris BoyrazSuneet Agarwal
Sep 21, 2016·Genes·Deanna Elise MacNeilChantal Autexier
Nov 2, 2016·Thorax·Susan K MathaiChristine Kim Garcia
Mar 16, 2017·Cold Spring Harbor Perspectives in Medicine·Caitlin M Roake, Steven E Artandi
Jan 8, 2017·Blood·Santhosh DhanrajYigal Dror
Jan 10, 2018·Cold Spring Harbor Perspectives in Biology·Adam M Heck, Jeffrey Wilusz
Nov 28, 2017·Molecular Genetics & Genomic Medicine·Jonathan Bizarro, U Thomas Meier
Apr 18, 2017·American Journal of Respiratory and Critical Care Medicine·Jonathan A KropskiJoy D Cogan
Dec 6, 2017·Annals of Internal Medicine·Sneh LataAli G Gharavi
Aug 2, 2017·Molecular and Cellular Biology·Siddharth Shukla, Roy Parker
Oct 30, 2018·Nucleic Acids Research·Tingting DengZhou Songyang
Aug 20, 2016·The European Respiratory Journal·Chad A NewtonChristine Kim Garcia
Dec 12, 2018·American Journal of Respiratory and Critical Care Medicine·David ZhangChristine Kim Garcia
Nov 22, 2016·Blood Advances·Fabien TouzotPatrick Revy
Sep 4, 2019·Expert Review of Hematology·Marena R Niewisch, Sharon A Savage
Oct 28, 2019·Wiley Interdisciplinary Reviews. RNA·Michael Robert Murphy, Frida Esther Kleiman
Jun 20, 2020·Blood Advances·Siddharth ShuklaLuis Francisco Zirnberger Batista
Jun 6, 2020·Genes & Development·Rea M Lardelli, Jens Lykke-Andersen
Aug 14, 2020·Wiley Interdisciplinary Reviews. RNA·Yong-Bin Yan
Jan 20, 2018·Nature Immunology·Martin Turner, Manuel D Díaz-Muñoz
May 28, 2020·The Journal of Biological Chemistry·Eden A DejeneEdward Seto
Apr 13, 2017·Nucleic Acids Research·Christian MontelleseMarie-Françoise O'Donohue
Jul 12, 2017·NPJ Genomic Medicine·Nicolas WaespeYigal Dror
May 18, 2018·F1000Research·Sharon A Savage
Dec 24, 2018·Nature Communications·Chi-Kang TsengPeter Baumann
Jul 6, 2019·EMBO Molecular Medicine·Maname BenyellesPatrick Revy
Nov 28, 2020·Osteoporosis International : a Journal Established As Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA·Z BelayaW Van Hul
Apr 23, 2020·Cell Stem Cell·Neha NagpalSuneet Agarwal
Sep 3, 2020·Stem Cells·Neha Nagpal, Suneet Agarwal

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