Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Leukodystrophy-associated POLR3A mutations down-regulate the RNA polymerase III transcript and important regulatory RNA BC200

ABSTRACT: Leukodystrophy-associated POLR3A mutations down-regulate the RNA polymerase III transcript and important regulatory RNA BC200

PROVIDER: PRJNA486660 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR7717410.fastq.gz	Fastqsanger.gz
	SRR7717420_1.fastq.gz	Fastqsanger.gz
	SRR7717420_2.fastq.gz	Fastqsanger.gz
	SRR7717430_1.fastq.gz	Fastqsanger.gz
	SRR7717430_2.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 50

Similar Datasets

Leukodystrophy-associated POLR3A mutations down-regulate the RNA polymerase III transcript and important regulatory RNA BC200

Project description:RNA polymerase III (Pol III) is an essential enzyme responsible for the synthesis of several small non-coding RNAs, a number of which are involved in mRNA translation. Recessive mutations in POLR3A, encoding the largest subunit of Pol III, cause POLR3-related hypomyelinating leukodystrophy (POLR3-HLD), characterized by deficient central nervous system myelination. Identification of the downstream effectors of pathogenic POLR3A mutations has been so far elusive. Here, we used CRISPR-Cas9 to introduce the POLR3A mutation c.2554A>G (p.M852V) into human cell lines and assessed its impact on Pol III biogenesis, nuclear import, DNA occupancy, transcription, and protein levels. Transcriptomic profiling uncovered a subset of transcripts vulnerable to Pol III hypofunction, including a global reduction in tRNA levels. The brain cytoplasmic BC200 RNA (BCYRN1), involved in translation regulation, was consistently affected in all our cellular models, including patient-derived fibroblasts. Genomic BC200 deletion in an oligodendroglial cell line led to major transcriptomic and proteomic changes, having a larger impact than those of POLR3A mutations. Upon differentiation, mRNA levels of the MBP gene, encoding myelin basic protein, were significantly decreased in POLR3A-mutant cells. Our findings provide the first evidence for impaired Pol III transcription in cellular models of POLR3-HLD and identify several candidate effectors, including BC200 RNA, having a potential role in oligodendrocyte biology and involvement in the disease.

2019-03-20 | GSE118739 | GEO

Leukodystrophy-associated <i>POLR3A</i> mutations down-regulate the RNA polymerase III transcript and important regulatory RNA <i>BC200</i>.

Project description: Not available

| S-EPMC6509492 | biostudies-literature

Recessive mutations in POLR1C cause a leukodystrophy by impairing biogenesis of RNA polymerase III

Project description:A small proportion of 4H (Hypomyelination, Hypodontia and Hypogonadotropic Hypogonadism) or RNA polymerase III (POLR3)-related leukodystrophy cases are negative for mutations in the previously identified causative genes POLR3A and POLR3B. Here, we report eight of these cases carrying recessive mutations in POLR1C, a gene encoding a shared POLR1 and POLR3 subunit, also mutated in some Treacher Collins syndrome (TCS) cases. Using shotgun proteomics and ChIP-sequencing we demonstrate that leukodystrophy causative mutations, but not TCS mutations, in POLR1C impair assembly and nuclear import of POLR3, but not POLR1, leading to decreased binding to POLR3 target genes. This study is the first to show that distinct mutations in a gene coding for a shared subunit of two RNA polymerases lead to selective modification of the enzymes' availability leading to two different clinical conditions and to shed some light on the pathophysiological mechanism of one of the most common hypomyelinating leukodystrophies, POLR3-related leukodystrophy.

2019-10-16 | PXD002154 | Pride

POLR3A ChIPseq

Project description:POLR3A ChIPseq

| PRJNA591570 | ENA

POLR3A ChIPseq

Project description:POLR3A ChIPseq in MDA-231 and MDA-LM2 cells

2022-11-25 | GSE140957 | GEO

polr3a mutant vs wild-type

Project description:We examined zebrafish with a mutation in polr3a, encoding the largest subunit of RNA Polymerase III. We then compared transcriptional responses of different cell types in the head of polr3a mutant zebrafish versus wild-type using a single cell RNA-seq approach.

2026-05-16 | GSE315895 | GEO

Mutations of POLR3A encoding a catalytic subunit of RNA polymerase Pol III cause a recessive hypomyelinating leukodystrophy.

Project description: Not available

| S-EPMC3169829 | biostudies-literature

Expanding the map of Pol III transcriptome: eCLIP and ROPE-seq of POLR3A

Project description:RNA polymerase III (Pol III) synthesizes noncoding RNAs essential for translation, RNA processing, and transcription regulation. Its activity aligns with cellular growth and nutrient availability, and its dysregulation is linked to diseases like breast cancer and leukodystrophy. Here we use eCLIP and ROPE-seq to identify short-lived Pol III transcripts

2026-07-09 | GSE337525 | GEO

polr3a mutant vs wild-type

Project description:polr3a mutant vs wild-type

| PRJNA1399746 | ENA

Dystonia in RNA Polymerase III-Related Leukodystrophy.

Project description: Not available

| S-EPMC6384176 | biostudies-literature