AustralieFrV1, Ncbi, Checkpoint, bibRecord, 002813

Recessive mutations in POLR1C cause a leukodystrophy by impairing biogenesis of RNA polymerase III

Identifieur interne : 002813 ( Ncbi/Checkpoint ); précédent : 002812; suivant : 002814

Recessive mutations in POLR1C cause a leukodystrophy by impairing biogenesis of RNA polymerase III

Auteurs : Isabelle Thiffault [Canada, États-Unis] ; Nicole I. Wolf [Pays-Bas] ; Diane Forget [Canada] ; Kether Guerrero [Canada] ; Luan T. Tran [Canada] ; Karine Choquet [Canada] ; Mathieu Lavallée-Adam [États-Unis] ; Christian Poitras [Canada] ; Bernard Brais [Canada] ; Grace Yoon [Canada] ; Laszlo Sztriha [Hongrie] ; Richard I. Webster [Australie] ; Dagmar Timmann [Allemagne] ; Bart P. Van De Warrenburg [Pays-Bas] ; Jürgen Seeger [Allemagne] ; Alíz Zimmermann [Hongrie] ; Adrienn Máté [Hongrie] ; Cyril Goizet [France] ; Eva Fung ; Marjo S. Van Der Knaap [Pays-Bas] ; Sébastien Fribourg [France] ; Adeline Vanderver [États-Unis] ; Cas Simons [Australie] ; Ryan J. Taft [États-Unis, Australie] ; John R. Yates Iii [États-Unis] ; Benoit Coulombe [Canada] ; Geneviève Bernard [Canada]

Source :

Nature Communications [ 2041-1723 ] ; 2015.

RBID : PMC:4506509

Descripteurs français

English descriptors

KwdEn :
- DNA-Directed RNA Polymerases (genetics), DNA-Directed RNA Polymerases (metabolism), Gene Expression Regulation, Enzymologic (physiology), Genes, Recessive, Genetic Predisposition to Disease, Hereditary Central Nervous System Demyelinating Diseases (genetics), Homozygote, Humans, Mutation, RNA Polymerase III (genetics), RNA Polymerase III (metabolism).
MESH :
- chemical , genetics : DNA-Directed RNA Polymerases, RNA Polymerase III.
- chemical , metabolism : DNA-Directed RNA Polymerases, RNA Polymerase III.
- genetics : Hereditary Central Nervous System Demyelinating Diseases.
- physiology : Gene Expression Regulation, Enzymologic.
- Genes, Recessive, Genetic Predisposition to Disease, Homozygote, Humans, Mutation.

Abstract

A small proportion of 4H (Hypomyelination, Hypodontia and Hypogonadotropic Hypogonadism) or RNA polymerase III (POLR3)-related leukodystrophy cases are negative for mutations in the previously identified causative genes POLR3A and POLR3B. Here we report eight of these cases carrying recessive mutations in POLR1C, a gene encoding a shared POLR1 and POLR3 subunit, also mutated in some Treacher Collins syndrome (TCS) cases. Using shotgun proteomics and ChIP sequencing, we demonstrate that leukodystrophy-causative mutations, but not TCS mutations, in POLR1C impair assembly and nuclear import of POLR3, but not POLR1, leading to decreased binding to POLR3 target genes. This study is the first to show that distinct mutations in a gene coding for a shared subunit of two RNA polymerases lead to selective modification of the enzymes' availability leading to two different clinical conditions and to shed some light on the pathophysiological mechanism of one of the most common hypomyelinating leukodystrophies, POLR3-related leukodystrophy.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4506509

DOI: 10.1038/ncomms8623
PubMed: 26151409
PubMed Central: 4506509

Affiliations:

Allemagne, Australie, Canada, France, Hongrie, Pays-Bas, États-Unis

Links to Exploration step

PMC:4506509

Le document en format XML

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<author><name sortKey="Yates Iii, John R" sort="Yates Iii, John R" uniqKey="Yates Iii J" first="John R." last="Yates Iii">John R. Yates Iii</name>
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<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<affiliation wicri:level="1"><nlm:aff id="a26"><institution>Department of Biochemistry, Université de Montréal, Pavillon Roger-Gaudry</institution>
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<country xml:lang="fr">Canada</country>
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<author><name sortKey="Bernard, Genevieve" sort="Bernard, Genevieve" uniqKey="Bernard G" first="Geneviève" last="Bernard">Geneviève Bernard</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Recessive mutations in <italic>POLR1C</italic>
 cause a leukodystrophy by impairing biogenesis of RNA polymerase III</title>
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.</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a3"><institution>Center for Pediatric Genomic Medicine, Children's Mercy Hospital</institution>
, 2420 Pershing Road, Suite 421, Kansas City, Missouri 64108,<country>USA</country>
.</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Wolf, Nicole I" sort="Wolf, Nicole I" uniqKey="Wolf N" first="Nicole I." last="Wolf">Nicole I. Wolf</name>
<affiliation wicri:level="1"><nlm:aff id="a4"><institution>Department of Child Neurology, VU University Medical Center, Neuroscience Campus Amsterdam</institution>
, Amsterdam 1081 HZ,<country>The Netherlands</country>
.</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Forget, Diane" sort="Forget, Diane" uniqKey="Forget D" first="Diane" last="Forget">Diane Forget</name>
<affiliation wicri:level="1"><nlm:aff id="a5"><institution>Translational Proteomics Laboratory, Institut de recherches cliniques de Montréal (IRCM)</institution>
, 110 avenue des Pins ouest, Montréal, Québec H2W 1R7,<country>Canada</country>
.</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Guerrero, Kether" sort="Guerrero, Kether" uniqKey="Guerrero K" first="Kether" last="Guerrero">Kether Guerrero</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Department of Neurology and Neurosurgery, McGill University, Department of Medical Genetics, Montreal Children's Hospital, Research Institute of the McGill University Health Center</institution>
, 1001 boul Décarie, Montreal, Quebec H4A 3J1,<country>Canada</country>
.</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Tran, Luan T" sort="Tran, Luan T" uniqKey="Tran L" first="Luan T." last="Tran">Luan T. Tran</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Department of Neurology and Neurosurgery, McGill University, Department of Medical Genetics, Montreal Children's Hospital, Research Institute of the McGill University Health Center</institution>
, 1001 boul Décarie, Montreal, Quebec H4A 3J1,<country>Canada</country>
.</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Choquet, Karine" sort="Choquet, Karine" uniqKey="Choquet K" first="Karine" last="Choquet">Karine Choquet</name>
<affiliation wicri:level="1"><nlm:aff id="a6"><institution>Neurogenetics of Motion Laboratory, Montreal Neurological Institute</institution>
, 3801 University Street, McGill University, Montreal, Quebec H3A 2B4,<country>Canada</country>
.</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Lavallee Adam, Mathieu" sort="Lavallee Adam, Mathieu" uniqKey="Lavallee Adam M" first="Mathieu" last="Lavallée-Adam">Mathieu Lavallée-Adam</name>
<affiliation wicri:level="1"><nlm:aff id="a7"><institution>Department of Chemical Physiology, The Scripps Research Institute</institution>
, 10550 North Torrey Pines Road SR302, La Jolla, California 92037,<country>USA</country>
.</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Poitras, Christian" sort="Poitras, Christian" uniqKey="Poitras C" first="Christian" last="Poitras">Christian Poitras</name>
<affiliation wicri:level="1"><nlm:aff id="a5"><institution>Translational Proteomics Laboratory, Institut de recherches cliniques de Montréal (IRCM)</institution>
, 110 avenue des Pins ouest, Montréal, Québec H2W 1R7,<country>Canada</country>
.</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Brais, Bernard" sort="Brais, Bernard" uniqKey="Brais B" first="Bernard" last="Brais">Bernard Brais</name>
<affiliation wicri:level="1"><nlm:aff id="a6"><institution>Neurogenetics of Motion Laboratory, Montreal Neurological Institute</institution>
, 3801 University Street, McGill University, Montreal, Quebec H3A 2B4,<country>Canada</country>
.</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Yoon, Grace" sort="Yoon, Grace" uniqKey="Yoon G" first="Grace" last="Yoon">Grace Yoon</name>
<affiliation wicri:level="1"><nlm:aff id="a8"><institution>Division of Neurology and Clinical and Metabolic Genetics, the Hospital for Sick Children, University of Toronto</institution>
, 555 University Avenue, Toronto, Ontario M5G 1X8,<country>Canada</country>
.</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Sztriha, Laszlo" sort="Sztriha, Laszlo" uniqKey="Sztriha L" first="Laszlo" last="Sztriha">Laszlo Sztriha</name>
<affiliation wicri:level="1"><nlm:aff id="a9"><institution>Department of Paediatrics, Faculty of Medicine, University of Szeged</institution>
, Temesvári krt. 35-37, Szeged H-6726,<country>Hungary</country>
.</nlm:aff>
<country xml:lang="fr">Hongrie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Webster, Richard I" sort="Webster, Richard I" uniqKey="Webster R" first="Richard I." last="Webster">Richard I. Webster</name>
<affiliation wicri:level="1"><nlm:aff id="a10"><institution>T.Y. Nelson Department of Neurology and Neurosurgery, The Children's Hospital at Westmead</institution>
, Locked Bag 4001, Westmead, New South Wales 2145,<country>Australia</country>
.</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a11"><institution>Institute for Neuroscience and Muscle Research, The Children's Hospital at Westmead</institution>
, Locked Bag 4001, Westmead New South Wales 2145,<country>Australia</country>
.</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Timmann, Dagmar" sort="Timmann, Dagmar" uniqKey="Timmann D" first="Dagmar" last="Timmann">Dagmar Timmann</name>
<affiliation wicri:level="1"><nlm:aff id="a12"><institution>Department of Neurology, University Clinic Essen, University of Duisburg-Essen</institution>
, Hufelandstrasse 55, 45147 Essen,<country>Germany</country>
.</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Van De Warrenburg, Bart P" sort="Van De Warrenburg, Bart P" uniqKey="Van De Warrenburg B" first="Bart P." last="Van De Warrenburg">Bart P. Van De Warrenburg</name>
<affiliation wicri:level="1"><nlm:aff id="a13"><institution>Department of Neurology, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center</institution>
, PO Box 9101, Nijmegen 6500 HB,<country>The Netherlands</country>
.</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Seeger, Jurgen" sort="Seeger, Jurgen" uniqKey="Seeger J" first="Jürgen" last="Seeger">Jürgen Seeger</name>
<affiliation wicri:level="1"><nlm:aff id="a14"><institution>Department of Pediatrics and Adolescent Medicine, Deutsche KlinikfürDiagnostik</institution>
, Wiesbaden 65191,<country>Germany</country>
.</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Zimmermann, Aliz" sort="Zimmermann, Aliz" uniqKey="Zimmermann A" first="Alíz" last="Zimmermann">Alíz Zimmermann</name>
<affiliation wicri:level="1"><nlm:aff id="a9"><institution>Department of Paediatrics, Faculty of Medicine, University of Szeged</institution>
, Temesvári krt. 35-37, Szeged H-6726,<country>Hungary</country>
.</nlm:aff>
<country xml:lang="fr">Hongrie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Mate, Adrienn" sort="Mate, Adrienn" uniqKey="Mate A" first="Adrienn" last="Máté">Adrienn Máté</name>
<affiliation wicri:level="1"><nlm:aff id="a15"><institution>Department of Neurosurgery, Faculty of Medicine, University of Szeged</institution>
, 6 Semmelweis Street, Szeged H-6725,<country>Hungary</country>
.</nlm:aff>
<country xml:lang="fr">Hongrie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Goizet, Cyril" sort="Goizet, Cyril" uniqKey="Goizet C" first="Cyril" last="Goizet">Cyril Goizet</name>
<affiliation wicri:level="1"><nlm:aff id="a16"><institution>Service de Génétique, Hôpital Pellegrin, CHU Bordeaux and University Bordeaux, Laboratoire MRGM (EA4576)</institution>
, Bordeaux 33076,<country>France</country>
.</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Fung, Eva" sort="Fung, Eva" uniqKey="Fung E" first="Eva" last="Fung">Eva Fung</name>
<affiliation><nlm:aff id="a17"><institution>Department of Paediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital</institution>
, Shatin, Hong Kong,<country>SAR China</country>
.</nlm:aff>
<wicri:noCountry code="nlm country">SAR China</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Van Der Knaap, Marjo S" sort="Van Der Knaap, Marjo S" uniqKey="Van Der Knaap M" first="Marjo S." last="Van Der Knaap">Marjo S. Van Der Knaap</name>
<affiliation wicri:level="1"><nlm:aff id="a4"><institution>Department of Child Neurology, VU University Medical Center, Neuroscience Campus Amsterdam</institution>
, Amsterdam 1081 HZ,<country>The Netherlands</country>
.</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Fribourg, Sebastien" sort="Fribourg, Sebastien" uniqKey="Fribourg S" first="Sébastien" last="Fribourg">Sébastien Fribourg</name>
<affiliation wicri:level="1"><nlm:aff id="a18"><institution>Université de Bordeaux, Institut Européen de Chimie et Biologie, ARNA Laboratory</institution>
, Pessac F-33607,<country>France</country>
.</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a19"><institution>Institut National de la Santé Et de la Recherche Médicale, INSERM—U869, ARNA Laboratory</institution>
, Bordeaux F-33000,<country>France</country>
.</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Vanderver, Adeline" sort="Vanderver, Adeline" uniqKey="Vanderver A" first="Adeline" last="Vanderver">Adeline Vanderver</name>
<affiliation wicri:level="1"><nlm:aff id="a20"><institution>Center for Genetic Medicine Research, Children's National</institution>
, 111 Michigan Avenue Northwest, Washington, District of Columbia 20010,<country>USA</country>
.</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a21"><institution>Department of Neurology, Children's National</institution>
, 111 Michigan Avenue Northwest, Washington, District of Columbia 20010,<country>USA</country>
.</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a22"><institution>George Washington University, School of Medicine</institution>
, Washington, District of Columbia 20052,<country>USA</country>
.</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Simons, Cas" sort="Simons, Cas" uniqKey="Simons C" first="Cas" last="Simons">Cas Simons</name>
<affiliation wicri:level="1"><nlm:aff id="a23"><institution>Institute for Molecular Bioscience, University of Queensland</institution>
, Brisbane, Queensland 4072,<country>Australia</country>
.</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Taft, Ryan J" sort="Taft, Ryan J" uniqKey="Taft R" first="Ryan J." last="Taft">Ryan J. Taft</name>
<affiliation wicri:level="1"><nlm:aff id="a22"><institution>George Washington University, School of Medicine</institution>
, Washington, District of Columbia 20052,<country>USA</country>
.</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a23"><institution>Institute for Molecular Bioscience, University of Queensland</institution>
, Brisbane, Queensland 4072,<country>Australia</country>
.</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a24"><institution>Departments of Integrative Systems Biology and Pediatrics, School of Medicine and Health Sciences, The George Washington University</institution>
, Washington, District of Columbia 20037,<country>USA</country>
.</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a25"><institution>Illumina Inc.</institution>
, 5200 Illumina Way, San Diego, California 92122,<country>USA</country>
.</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Yates Iii, John R" sort="Yates Iii, John R" uniqKey="Yates Iii J" first="John R." last="Yates Iii">John R. Yates Iii</name>
<affiliation wicri:level="1"><nlm:aff id="a7"><institution>Department of Chemical Physiology, The Scripps Research Institute</institution>
, 10550 North Torrey Pines Road SR302, La Jolla, California 92037,<country>USA</country>
.</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Coulombe, Benoit" sort="Coulombe, Benoit" uniqKey="Coulombe B" first="Benoit" last="Coulombe">Benoit Coulombe</name>
<affiliation wicri:level="1"><nlm:aff id="a5"><institution>Translational Proteomics Laboratory, Institut de recherches cliniques de Montréal (IRCM)</institution>
, 110 avenue des Pins ouest, Montréal, Québec H2W 1R7,<country>Canada</country>
.</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a26"><institution>Department of Biochemistry, Université de Montréal, Pavillon Roger-Gaudry</institution>
, CP 6128, Succ Centre-Ville, Montreal, Québec H3C 3J7,<country>Canada</country>
.</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Bernard, Genevieve" sort="Bernard, Genevieve" uniqKey="Bernard G" first="Geneviève" last="Bernard">Geneviève Bernard</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Department of Neurology and Neurosurgery, McGill University, Department of Medical Genetics, Montreal Children's Hospital, Research Institute of the McGill University Health Center</institution>
, 1001 boul Décarie, Montreal, Quebec H4A 3J1,<country>Canada</country>
.</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series><title level="j">Nature Communications</title>
<idno type="eISSN">2041-1723</idno>
<imprint><date when="2015">2015</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>DNA-Directed RNA Polymerases (genetics)</term>
<term>DNA-Directed RNA Polymerases (metabolism)</term>
<term>Gene Expression Regulation, Enzymologic (physiology)</term>
<term>Genes, Recessive</term>
<term>Genetic Predisposition to Disease</term>
<term>Hereditary Central Nervous System Demyelinating Diseases (genetics)</term>
<term>Homozygote</term>
<term>Humans</term>
<term>Mutation</term>
<term>RNA Polymerase III (genetics)</term>
<term>RNA Polymerase III (metabolism)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>DNA-directed RNA polymerases (génétique)</term>
<term>DNA-directed RNA polymerases (métabolisme)</term>
<term>Gènes récessifs</term>
<term>Homozygote</term>
<term>Humains</term>
<term>Maladies démyélinisantes héréditaires du système nerveux central (génétique)</term>
<term>Mutation</term>
<term>Prédisposition génétique à une maladie</term>
<term>RNA polymerase III (génétique)</term>
<term>RNA polymerase III (métabolisme)</term>
<term>Régulation de l'expression des gènes codant pour des enzymes (physiologie)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>DNA-Directed RNA Polymerases</term>
<term>RNA Polymerase III</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>DNA-Directed RNA Polymerases</term>
<term>RNA Polymerase III</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Hereditary Central Nervous System Demyelinating Diseases</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>DNA-directed RNA polymerases</term>
<term>Maladies démyélinisantes héréditaires du système nerveux central</term>
<term>RNA polymerase III</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>DNA-directed RNA polymerases</term>
<term>RNA polymerase III</term>
</keywords>
<keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Régulation de l'expression des gènes codant pour des enzymes</term>
</keywords>
<keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Gene Expression Regulation, Enzymologic</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Genes, Recessive</term>
<term>Genetic Predisposition to Disease</term>
<term>Homozygote</term>
<term>Humans</term>
<term>Mutation</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Gènes récessifs</term>
<term>Homozygote</term>
<term>Humains</term>
<term>Mutation</term>
<term>Prédisposition génétique à une maladie</term>
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<front><div type="abstract" xml:lang="en"><p>A small proportion of 4H (Hypomyelination, Hypodontia and Hypogonadotropic Hypogonadism) or RNA polymerase III (POLR3)-related leukodystrophy cases are negative for mutations in the previously identified causative genes <italic>POLR3A</italic>
 and <italic>POLR3B</italic>
. Here we report eight of these cases carrying recessive mutations in <italic>POLR1C</italic>
, a gene encoding a shared POLR1 and POLR3 subunit, also mutated in some Treacher Collins syndrome (TCS) cases. Using shotgun proteomics and ChIP sequencing, we demonstrate that leukodystrophy-causative mutations, but not TCS mutations, in <italic>POLR1C</italic>
 impair assembly and nuclear import of POLR3, but not POLR1, leading to decreased binding to POLR3 target genes. This study is the first to show that distinct mutations in a gene coding for a shared subunit of two RNA polymerases lead to selective modification of the enzymes' availability leading to two different clinical conditions and to shed some light on the pathophysiological mechanism of one of the most common hypomyelinating leukodystrophies, POLR3-related leukodystrophy.</p>
</div>
</front>
<back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Schiffmann, R" uniqKey="Schiffmann R">R. Schiffmann</name>
</author>
<author><name sortKey="Van Der Knaap, M S" uniqKey="Van Der Knaap M">M. S. van der Knaap</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Schiffmann, R" uniqKey="Schiffmann R">R. Schiffmann</name>
</author>
<author><name sortKey="Van Der Knaap, M S" uniqKey="Van Der Knaap M">M. S. van der Knaap</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bernard, G" uniqKey="Bernard G">G. Bernard</name>
</author>
<author><name sortKey="Vanderver, A" uniqKey="Vanderver A">A. Vanderver</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bernard, G" uniqKey="Bernard G">G. Bernard</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Tetreault, M" uniqKey="Tetreault M">M. Tetreault</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Saitsu, H" uniqKey="Saitsu H">H. Saitsu</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Terao, Y" uniqKey="Terao Y">Y. Terao</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Potic, A" uniqKey="Potic A">A. Potic</name>
</author>
<author><name sortKey="Brais, B" uniqKey="Brais B">B. Brais</name>
</author>
<author><name sortKey="Choquet, K" uniqKey="Choquet K">K. Choquet</name>
</author>
<author><name sortKey="Schiffmann, R" uniqKey="Schiffmann R">R. Schiffmann</name>
</author>
<author><name sortKey="Bernard, G" uniqKey="Bernard G">G. Bernard</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Daoud, H" uniqKey="Daoud H">H. Daoud</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Wolf, N I" uniqKey="Wolf N">N. I. Wolf</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Steenweg, M E" uniqKey="Steenweg M">M. E. Steenweg</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="La Piana, R" uniqKey="La Piana R">R. La Piana</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Dumay Odelot, H" uniqKey="Dumay Odelot H">H. Dumay-Odelot</name>
</author>
<author><name sortKey="Durrieu Gaillard, S" uniqKey="Durrieu Gaillard S">S. Durrieu-Gaillard</name>
</author>
<author><name sortKey="Da, S D" uniqKey="Da S">S. D. Da</name>
</author>
<author><name sortKey="Roeder, R G" uniqKey="Roeder R">R. G. Roeder</name>
</author>
<author><name sortKey="Teichmann, M" uniqKey="Teichmann M">M. Teichmann</name>
</author>
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<biblStruct><analytic><author><name sortKey="Dauwerse, J G" uniqKey="Dauwerse J">J. G. Dauwerse</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Miron Garcia, M C" uniqKey="Miron Garcia M">M. C. Miron-Garcia</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Jeronimo, C" uniqKey="Jeronimo C">C. Jeronimo</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Forget, D" uniqKey="Forget D">D. Forget</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Forget, D" uniqKey="Forget D">D. Forget</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Forget, D" uniqKey="Forget D">D. Forget</name>
</author>
<author><name sortKey="Cloutier, P" uniqKey="Cloutier P">P. Cloutier</name>
</author>
<author><name sortKey="Domecq, C" uniqKey="Domecq C">C. Domecq</name>
</author>
<author><name sortKey="Coulombe, B" uniqKey="Coulombe B">B. Coulombe</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Cloutier, P" uniqKey="Cloutier P">P. Cloutier</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Boulon, S" uniqKey="Boulon S">S. Boulon</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Canella, D" uniqKey="Canella D">D. Canella</name>
</author>
<author><name sortKey="Praz, V" uniqKey="Praz V">V. Praz</name>
</author>
<author><name sortKey="Reina, J H" uniqKey="Reina J">J. H. Reina</name>
</author>
<author><name sortKey="Cousin, P" uniqKey="Cousin P">P. Cousin</name>
</author>
<author><name sortKey="Hernandez, N" uniqKey="Hernandez N">N. Hernandez</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kutter, C" uniqKey="Kutter C">C. Kutter</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Raha, D" uniqKey="Raha D">D. Raha</name>
</author>
</analytic>
</biblStruct>
<biblStruct></biblStruct>
<biblStruct><analytic><author><name sortKey="Scheper, G C" uniqKey="Scheper G">G. C. Scheper</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Steenweg, M E" uniqKey="Steenweg M">M. E. Steenweg</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Gotz, A" uniqKey="Gotz A">A. Gotz</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Taft, R J" uniqKey="Taft R">R. J. Taft</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Wolf, N I" uniqKey="Wolf N">N. I. Wolf</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bilguvar, K" uniqKey="Bilguvar K">K. Bilguvar</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Depristo, M A" uniqKey="Depristo M">M. A. DePristo</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Mckenna, A" uniqKey="Mckenna A">A. McKenna</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Li, H" uniqKey="Li H">H. Li</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Cheng, A Y" uniqKey="Cheng A">A. Y. Cheng</name>
</author>
<author><name sortKey="Teo, Y Y" uniqKey="Teo Y">Y. Y. Teo</name>
</author>
<author><name sortKey="Ong, R T" uniqKey="Ong R">R. T. Ong</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Cleary, J G" uniqKey="Cleary J">J. G. Cleary</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Cingolani, P" uniqKey="Cingolani P">P. Cingolani</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Mellacheruvu, D" uniqKey="Mellacheruvu D">D. Mellacheruvu</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Chen, G I" uniqKey="Chen G">G. I. Chen</name>
</author>
<author><name sortKey="Gingras, A C" uniqKey="Gingras A">A. C. Gingras</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Lavallee Adam, M" uniqKey="Lavallee Adam M">M. Lavallee-Adam</name>
</author>
</analytic>
</biblStruct>
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<author><name sortKey="Pappin, D J" uniqKey="Pappin D">D. J. Pappin</name>
</author>
<author><name sortKey="Creasy, D M" uniqKey="Creasy D">D. M. Creasy</name>
</author>
<author><name sortKey="Cottrell, J S" uniqKey="Cottrell J">J. S. Cottrell</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Benjamini, Y" uniqKey="Benjamini Y">Y. Benjamini</name>
</author>
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</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Langlais, D" uniqKey="Langlais D">D. Langlais</name>
</author>
<author><name sortKey="Couture, C" uniqKey="Couture C">C. Couture</name>
</author>
<author><name sortKey="Sylvain Drolet, G" uniqKey="Sylvain Drolet G">G. Sylvain-Drolet</name>
</author>
<author><name sortKey="Drouin, J" uniqKey="Drouin J">J. Drouin</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Lohse, M" uniqKey="Lohse M">M. Lohse</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Langmead, B" uniqKey="Langmead B">B. Langmead</name>
</author>
<author><name sortKey="Salzberg, S L" uniqKey="Salzberg S">S. L. Salzberg</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Zhang, Y" uniqKey="Zhang Y">Y. Zhang</name>
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</biblStruct>
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</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Harrow, J" uniqKey="Harrow J">J. Harrow</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Lowe, T M" uniqKey="Lowe T">T. M. Lowe</name>
</author>
<author><name sortKey="Eddy, S R" uniqKey="Eddy S">S. R. Eddy</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Chan, P P" uniqKey="Chan P">P. P. Chan</name>
</author>
<author><name sortKey="Lowe, T M" uniqKey="Lowe T">T. M. Lowe</name>
</author>
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<biblStruct><analytic><author><name sortKey="Thorvaldsdottir, H" uniqKey="Thorvaldsdottir H">H. Thorvaldsdottir</name>
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<author><name sortKey="Robinson, J T" uniqKey="Robinson J">J. T. Robinson</name>
</author>
<author><name sortKey="Mesirov, J P" uniqKey="Mesirov J">J. P. Mesirov</name>
</author>
</analytic>
</biblStruct>
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</author>
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</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Wild, T" uniqKey="Wild T">T. Wild</name>
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</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Alla, R K" uniqKey="Alla R">R. K. Alla</name>
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<author><name sortKey="Cairns, B R" uniqKey="Cairns B">B. R. Cairns</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Cong, R" uniqKey="Cong R">R. Cong</name>
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<affiliations><list><country><li>Allemagne</li>
<li>Australie</li>
<li>Canada</li>
<li>France</li>
<li>Hongrie</li>
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   |texte=   Recessive mutations in POLR1C cause a leukodystrophy by impairing biogenesis of RNA polymerase III
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Serveur d'exploration sur les relations entre la France et l'Australie

Recessive mutations in POLR1C cause a leukodystrophy by impairing biogenesis of RNA polymerase III

Recessive mutations in POLR1C cause a leukodystrophy by impairing biogenesis of RNA polymerase III

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	Serveur d'exploration sur les relations entre la France et l'Australie
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