PXD025029-1

PXD025029 is an original dataset announced via ProteomeXchange.

Title	A disease-linked lncRNA mutation in RNase MRP inhibits ribosome synthesis
Description	Mutations 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.
HostingRepository	PRIDE
AnnounceDate	2021-03-30
AnnouncementXML	Submission_2021-03-30_11:41:27.706.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Nic Robertson
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-03-26 04:46:43	ID requested
⏵ 1	2021-03-30 11:41:28	announced

Dataset with its publication pending

submitter keyword: Protein-RNA interaction

RNA-binding sites

UV crosslinking

mass spectrometry

genetic disease

Cartilage Hair Hypoplasia

ribosome synthesis

T cell activation

David Tollervey
contact affiliation	WCCB, University of Edinburgh
contact email	d.tollervey@ed.ac.uk
lab head
Nic Robertson
contact affiliation	WCCB, University of Edinburgh
contact email	nic.robertson@ed.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD025029
     1. Label: PRIDE project
     2. Name: A disease-linked lncRNA mutation in RNase MRP inhibits ribosome synthesis