Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA219492 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR990360.fastq.gz | Fastqsanger.gz |
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Project 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.
2021-03-30 | PXD025029 | Pride
Project 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.
2021-12-14 | GSE190787 | GEO
Project 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.
2021-03-29 | GSE171020 | GEO
Project 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.
2021-03-29 | GSE171019 | GEO
Project description:RNase P and RNase MRP are evolutionarily-related ribonucleoprotein complexes that share common protein subunits, but carry out distinct site-specific endonuclease activities. Here, we identify two RNase MRP-specific proteins C18orf21 (RMP24) and Nepro (RMP64). C18orf21 contains a structurally similar N-terminal domain to Rpp21, but has a distinct subcellular localization and RNA-binding specificity, allowing C18orf21 to uniquely associate with RNase MRP. We ectopically express C18orf21 (RNase MRP specific), Nepro (RNase MRP specific), Rpp21 (RNase P specific), and Rpp14 (shared subunit), with a C-terminal GFP and performed RIP-seq to identify bound RNAs. Our data provide a model to understand C18orf21 physical interactions along with its role in ribosomal RNA processing. In addition to this, we knock out C18orf21, Rpp21, and Rpp14 and analyze their transcriptome. We additionally analyze rRNA intermediates in knockout cells.
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Project description:Mutations in the RMRP gene are the origin of cartilage-hair hypoplasia. Cartilage-hair hypoplasia is associated with severe dwarfism caused by impaired skeletal development. However, it is not clear why mutations in the RMRP gene lead to skeletal dysplasia. Viperin is a known substrate of RMRP. Since chondrogenic differentiation of the growth plate is required for development of the long bones, we hypothesized that viperin functions as a chondrogenic regulator downstream of RMRP. Viperin protein is expressed throughout the stages of chondrogenic differentiation in vivo. Viperin gene expression is increased during knockdown of Rmrp RNA in the ATDC5 model for chondrogenic differentiation. Viperin is expressed during ATDC5 chondrogenic differentiation. Viperin knockdown reduces, while viperin overexpression increases overall protein secretion, with CXCL10 identified as a potential target via mass spectrometry-proteomics. CXCL10 protein expression is reduced during knockdown and increased during overexpression of viperin and CXCL10 protein expression coincides with viperin expression in ATDC5 chondrogenic differentiation. Viperin knockdown induces, while viperin overexpression reduces TGFβ activity. Furthermore, viperin knockdown conditioned media increases, while viperin overexpression conditioned media reduces chondrogenic differentiation of ATDC5 cells. TGFβ target genes Pai1 and Smad7 are increased during knockdown and reduced during overexpression of viperin. Moreover, TGFβ activity is reduced when differentiating ATDC5 cells are exposed to CXCL10 and, acting as a viperin overexpression mimic, CXCL10 similarly reduces chondrogenic differentiation of ATDC5. Lastly, we show that in CHH patient cells, RMRP expression is reduced and viperin expression is increased, coinciding with reduced chondrogenic differentiation and increased CXCL10 expression, possibly explaining the CHH phenotype. Together our data show that viperin may play a pivotal role in chondrogenic differentiation, with potential consequences for cartilage-hair hypoplasia pathobiology.
2019-02-15 | PXD006999 | Pride
Project description:Ribonuclease (RNase) MRP is a conserved RNA-based enzyme that is essential for maturation of ribosomal RNA (rRNA) in eukaryotes. However, the composition and RNA substrate specificity of this multisubunit ribonucleoprotein complex in higher eukaryotes remain a mystery. Here, we identify NEPRO and C18ORF21 as constitutive subunits of metazoan RNase MRP. Both proteins are specific to RNase MRP and are the only ones distinguishing this enzyme from the closely related RNase P, which selectively cleaves transfer RNA-like substrates. We find that NEPRO and C18ORF21 each form a complex with all other subunits of RNase MRP, stabilize its catalytic RNA, and are required for rRNA maturation and cell proliferation. We harness our discovery to identify a full suite of in vivo RNA targets of each enzyme, including positions of potential cleavage sites at nucleotide resolution. These findings resolve the general composition of metazoan RNase MRP, illuminate its RNA binding specificity, and provide valuable assets for functional exploration of this essential eukaryotic enzyme.
2025-08-05 | GSE290995 | GEO
Project description:Mechanistic studies have revealed ribonuclease (RNase) MRP, a conserved RNA-based enzyme, is crucial for the maturation of ribosomal RNA in eukaryotes. However, the composition and RNA substrate specificity of this multisubunit ribonucleoprotein complex in higher eukaryotes remain unknown. Here, we identify NEPRO and C18ORF21 as constitutive subunits of metazoan RNase MRP. Both proteins are specific to RNase MRP and are the only ones distinguishing this enzyme from the closely related RNase P, which selectively cleaves transfer RNA-like substrates. We find that NEPRO and C18ORF21 each form a complex with all other subunits of RNase MRP, stabilize its catalytic RNA, and are required for rRNA maturation and cell proliferation. We harness our discovery to identify a full suite of in vivo RNA targets of each enzyme, including positions of potential cleavage sites at nucleotide resolution. In Summary, this project shows the general composition of metazoan RNase MRP, illuminate its RNA binding specificity, and provide valuable assets for functional exploration of this essential eukaryotic enzyme.
2025-09-15 | PXD061658 | Pride
Project description:To identify mRNA substrates for the human RNase MRP complex, we examined the effects of siRNA-mediated depletion of RNase MRP (and RNase P) on the transcriptome of HEp-2 cells. The expression of two RNase MRP protein components, hPop1 and Rpp40, was knocked-down and after 48 hours mRNA was isolated from these cells as well as from cells transfected with an siRNA targeting the GFP mRNA (siEGFP), which was used as a control. The expression levels of mRNAs were analyzed on a genome-wide scale using 21K microarrays.
2011-04-01 | E-TABM-981 | biostudies-arrayexpress