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PXD025029-1

PXD025029 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleA disease-linked lncRNA mutation in RNase MRP inhibits ribosome synthesis
DescriptionMutations in the human RMRP gene cause Cartilage Hair Hypoplasia (CHH), an autosomal recessive disorder characterized by skeletal abnormalities and impaired T-cell activation. RMRP encodes a non-coding RNA, which forms the core of the RNase MRP ribonucleoprotein complex. In budding yeast, RMRP cleaves a specific site in the pre-ribosomal RNA (pre-rRNA) during ribosome synthesis. CRISPR-mediated disruption of RMRP in human cells lines caused growth arrest, with pre-rRNA accumulation. Here, we analyzed disease-relevant primary cells, showing that mutations in RMRP impair mouse T cell activation and delay pre-rRNA processing. Analysis of pre-rRNA processing in patient-derived human fibroblasts with CHH-linked mutations showed a similar pattern of processing delay. Human cells engineered with the most common CHH mutation (70AG in RMRP) show specifically impaired pre-rRNA processing, resulting in reduced mature rRNA and a reduced ratio of cytosolic to mitochondrial ribosomes. Moreover, the 70AG mutation caused a reduction in intact RNase MRP complexes. Together, these results indicate that CHH is a ribosomopathy, and the first human disorder of rRNA processing to be described.
HostingRepositoryPRIDE
AnnounceDate2021-03-30
AnnouncementXMLSubmission_2021-03-30_11:41:27.706.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterNic Robertson
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-03-26 04:46:43ID requested
12021-03-30 11:41:28announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Protein-RNA interaction
RNA-binding sites
UV crosslinking
mass spectrometry
genetic disease
Cartilage Hair Hypoplasia
ribosome synthesis
T cell activation
Contact List
David Tollervey
contact affiliationWCCB, University of Edinburgh
contact emaild.tollervey@ed.ac.uk
lab head
Nic Robertson
contact affiliationWCCB, University of Edinburgh
contact emailnic.robertson@ed.ac.uk
dataset submitter
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Dataset FTP location
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