PXD002154

PXD002154 is an original dataset announced via ProteomeXchange.

Title	Recessive mutations in POLR1C cause a leukodystrophy by impairing biogenesis of RNA polymerase III
Description	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.
HostingRepository	PRIDE
AnnounceDate	2019-10-16
AnnouncementXML	Submission_2019-10-16_08:08:46.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christian Poitras
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2015-05-08 01:23:08	ID requested
1	2019-10-16 07:54:58	announced
⏵ 2	2019-10-16 08:08:48	announced	2019-10-16: Updated publication reference for PubMed record(s): 26151409.

Thiffault I, Wolf NI, Forget D, Guerrero K, Tran LT, Choquet K, Lavall, é, e-Adam M, Poitras C, Brais B, Yoon G, Sztriha L, Webster RI, Timmann D, van de Warrenburg BP, Seeger J, Zimmermann A, M, á, t, é A, Goizet C, Fung E, van der Knaap MS, Fribourg S, Vanderver A, Simons C, Taft RJ, Yates JR, Coulombe B, Bernard G, Recessive mutations in POLR1C cause a leukodystrophy by impairing biogenesis of RNA polymerase III. Nat Commun, 6():7623(2015) [pubmed]

curator keyword: Biomedical

submitter keyword: Leukodystrophy, POLR1C, RNA polymerase III, Human

Benoit Coulombe
contact affiliation	Translational Proteomics, IRCM, Canada
contact email	benoit.coulombe@ircm.qc.ca
lab head
Christian Poitras
contact affiliation	Laboratory of Gene Transcription and Proteomics Discovery Platform, Institut de recherches cliniques de Montréal, 110 avenue des Pins Ouest, Montréal, QC H2W 1R7, Canada
contact email	christian.poitras@ircm.qc.ca
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/10/PXD002154

PRIDE project URI

• PRIDE
  1. PXD002154
     1. Label: PRIDE project
     2. Name: Recessive mutations in POLR1C cause a leukodystrophy by impairing biogenesis of RNA polymerase III