PXD034961

PXD034961 is an original dataset announced via ProteomeXchange.

Title	Riluzole partially restores RNA polymerase III complex assembly in cells expressing the leukodystrophy-causative variant POLR3B R103H
Description	The mechanism of assembly of RNA polymerase III (Pol III), the 17-subunit enzyme that synthesizes tRNAs, 5S rRNA, and other small-nuclear (sn) RNAs in eukaryotes, is not clearly understood. The recent discovery of the HSP90 co-chaperone PAQosome (Particle for Arrangement of Quaternary structure) revealed a function for this machinery in the biogenesis of nuclear RNA polymerases. However, the connection between Pol III subunits and the PAQosome during the assembly process remains unexplored. Here, we report the development of a mass spectrometry-based assay that allows the characterization of Pol III assembly. This assay was used to dissect the stages of Pol III assembly, to start defining the function of the PAQosome in this process, to dissect the assembly defects driven by the leukodystrophy-causative R103H substitution in POLR3B, and to discover that riluzole, an FDA-approved drug for alleviation of ALS symptoms, partly corrects these assembly defects. Together, these results shed new light on the mechanism and regulation of human nuclear Pol III biogenesis.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:36:58.169.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Maxime Pinard
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2022-06-29 15:05:24	ID requested
1	2023-03-10 20:21:36	announced
⏵ 2	2023-11-14 08:37:00	announced	2023-11-14: Updated project metadata.

Pinard M, Dastpeyman S, Poitras C, Bernard G, Gauthier MS, Coulombe B, Riluzole partially restores RNA polymerase III complex assembly in cells expressing the leukodystrophy-causative variant POLR3B R103H. Mol Brain, 15(1):98(2022) [pubmed]

submitter keyword: protein complex assembly,RNA polymerase III, mass spectrometry, PAQosome, riluzole, POLR3-related leukodystrophy, 4H leukodystrophy, drug repurposing

Benoit Coulombe
contact affiliation	Translational Proteomics Laboratory, Institut de recherches cliniques de Montréal (IRCM), Québec, Montréal, Canada. Departement of Biochemistry and Molecular Medicine, Université de Montréal, Québec, Montréal, Canada. (Laboratory Director)
contact email	benoit.coulombe@ircm.qc.ca
lab head
Maxime Pinard
contact affiliation	Institut de Recherches Cliniques de Montréal (IRCM)
contact email	Maxime.pinard@IRCM.qc.ca
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD034961
     1. Label: PRIDE project
     2. Name: Riluzole partially restores RNA polymerase III complex assembly in cells expressing the leukodystrophy-causative variant POLR3B R103H