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| Status |
Public on Mar 29, 2021 |
| Title |
A disease-linked lncRNA mutation in RNase MRP inhibits ribosome synthesis [human] |
| Organism |
Homo sapiens |
| Experiment type |
Other
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| Summary |
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.
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| Overall design |
Human K562 cells with FLAG-HIS-tagged protein components of the MRP/P complex were grown in normal media, and RNA:protein interactions stabilised with UVC irradiation. RNAs interacting with tagged proteins were purified by CRAC.
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| Contributor(s) |
Robertson N, Shchepachev V, Wright D, Turowski TW, Spanos C, Helwak A, Zamoyska R, Tollervey D |
| Citation(s) |
35115551 |
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| Submission date |
Mar 28, 2021 |
| Last update date |
Feb 23, 2022 |
| Contact name |
Nic Robertson |
| E-mail(s) |
[email protected]
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| Organization name |
University of Edinburgh
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| Department |
Tollervey Lab
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| Street address |
Swann Building, Max Born Crescent
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| City |
Edinburgh |
| ZIP/Postal code |
EH9 3BF |
| Country |
United Kingdom |
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| Platforms (1) |
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| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE171021 |
A disease-linked lncRNA mutation in RNase MRP inhibits ribosome synthesis |
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| Relations |
| BioProject |
PRJNA718111 |
| SRA |
SRP312510 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE171019_RAW.tar |
5.6 Mb |
(http)(custom) |
TAR (of BW) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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