Ontology highlight
ABSTRACT:
PROVIDER: PRJNA143639 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Mutations in either the mitochondrial or nuclear genomes are associated with a diverse group of human disorders characterized by impaired mitochondrial respiration. Within this group, an increasing number of mutations have been identified in nuclear genes involved in mitochondrial RNA biology. The TEFM gene codes for the mitochondrial transcription elongation factor responsible for enhancing the processivity of mitochondrial RNA polymerase, POLRMT. Here, we report for the first time that TEFM variants are associated with mitochondrial respiratory chain deficiency and a wide range of clinical presentations including neonatal lactic acidosis, epileptic encephalopathy, developmental delay, intellectual disability or mitochondrial myopathy with a treatable neuromuscular transmission defect. Mechanistically, we show that muscle samples and primary fibroblasts from the affected individuals have reduced levels of promoter distal mitochondrial RNA transcripts, consistent with decreased processivity of POLRMT when TEFM is dysfunctional. We provide further evidence for the pathogenicity of these variants by investigating mitochondrial transcription and proteomic changes in patient cells and muscle and by studying TEFM activity in an in vitro system. Finally, tefm knock-down in zebrafish embryos resulted in neuromuscular junction abnormalities and abnormal mitochondrial function, strengthening the genotype-phenotype correlation. In conclusion, our study highlights that TEFM regulates mitochondrial transcription elongation in human tissues and its defect results in variable, tissue specific neurological and neuromuscular symptoms.
2022-11-07 | PXD030427 | Pride
Project description:Nuclear Actin Regulates Inducible Transcription by Enhancing RNA Polymerase II Clustering
| PRJNA324642 | ENA
Project description:Transcription of mRNA in mammalian is mainly performed by RNA polymerase II (PolII). POLRMT is responsible for the production of cytoplasmic and nuclear form of mitochondrial RNA polymerase. The former (mtRNAP) participates in transcription of RNA in the mitochondria while the latter (spRNAP-IV) is responsible for some mRNA transcription in the nucleus. The nature and amount of genes transcribed by spRNAP-IV still remains unclear. Thus, we scanned for possible candidate genes by using Affymetrix. MCF-7 cell line was subjected to siRNA knockdown of either non-targeting, POLRMT, or PolII for 72 hours
2011-07-01 | E-GEOD-28503 | biostudies-arrayexpress
Project description:Transcription of mRNA in mammalian is mainly performed by RNA polymerase II (PolII). POLRMT is responsible for the production of cytoplasmic and nuclear form of mitochondrial RNA polymerase. The former (mtRNAP) participates in transcription of RNA in the mitochondria while the latter (spRNAP-IV) is responsible for some mRNA transcription in the nucleus. The nature and amount of genes transcribed by spRNAP-IV still remains unclear. Thus, we scanned for possible candidate genes by using Affymetrix.
2011-07-01 | GSE28444 | GEO
Project description:Transcription of mRNA in mammalian is mainly performed by RNA polymerase II (PolII). POLRMT is responsible for the production of cytoplasmic and nuclear form of mitochondrial RNA polymerase. The former (mtRNAP) participates in transcription of RNA in the mitochondria while the latter (spRNAP-IV) is responsible for some mRNA transcription in the nucleus. The nature and amount of genes transcribed by spRNAP-IV still remains unclear. Thus, we scanned for possible candidate genes by using Affymetrix.
2011-07-01 | GSE28503 | GEO
Project description:Transcription of mRNA in mammalian is mainly performed by RNA polymerase II (PolII). POLRMT is responsible for the production of cytoplasmic and nuclear form of mitochondrial RNA polymerase. The former (mtRNAP) participates in transcription of RNA in the mitochondria while the latter (spRNAP-IV) is responsible for some mRNA transcription in the nucleus. The nature and amount of genes transcribed by spRNAP-IV still remains unclear. Thus, we scanned for possible candidate genes by using Affymetrix.
2011-07-01 | GSE28502 | GEO
Project description:Nuclear actin has been demonstrated to be essential for optimal transcription, but the molecular mechanisms and direct binding partner for actin in the RNA polymerase complex have remained unknown. By using purified proteins in several biochemical assays, we demonstrate a direct and specific interaction between monomeric actin and Cdk9, the kinase subunit of the positive transcription elongation factor b (P-TEFb) required for RNA polymerase II (Pol II) pause-release. This interaction is not dependent on kinase activity of Cdk9 and is not involved with releasing P-TEFb from its inhibitor 7SK snRNP complex. Supporting the specific role for actin in the elongation phase of transcription, chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) reveals that actin interacts with genes only upon their active transcription elongation. This study therefore provides novel insights into the mechanisms by which actin facilitates the transcription process.
2023-09-01 | GSE239771 | GEO
Project description:Transcription of mRNA in mammalian is mainly performed by RNA polymerase II (PolII). POLRMT is responsible for the production of cytoplasmic and nuclear form of mitochondrial RNA polymerase. The former (mtRNAP) participates in transcription of RNA in the mitochondria while the latter (spRNAP-IV) is responsible for some mRNA transcription in the nucleus. The nature and amount of genes transcribed by spRNAP-IV still remains unclear. Thus, we scanned for possible candidate genes by using Affymetrix. HUVSMC cell line was treated with or without 0.3 uM of Triptolide (an inhibitor of PolII) for 24 hours to determine which genes are insensitive to triptolide treatment.
2011-07-01 | E-GEOD-28502 | biostudies-arrayexpress
Project description:Nuclear myosin 1c (NM1) is emerging as regulator of transcription and chromatin organization. Using a genome-wide approach we report here that NM1 binds across the mammalian genome with occupancy peaks at class II gene promoters, correlating with distributions of RNA Polymerase II (Pol II) and active epigenetic marks. We show that NM1 synergizes with polymerase-associated actin to maintain active Pol II at gene promoters. NM1 also co-localizes with the nucleosome remodeler SNF2h at class II promoters where they assemble together with WSTF as part of the B-WICH complex to remodel chromatin. Following B-WICH assembly, NM1 mediates physical recruitment of the histone acetyl transferase PCAF and the histone methyl transferase Set1/Ash2 to maintain and preserve H3K9acetylation and H3K4trimethylation for active transcription. We propose a novel genome-wide mechanism where myosin synergizes with Pol II-associated actin to link the polymerase machinery with permissive chromatin for transcription activation. Association of nuclear myosin 1 (NM1) with the genome in mouse embryonic fibroblasts
2015-05-04 | E-GEOD-66542 | biostudies-arrayexpress
Project description:Transcription of mRNA in mammalian is mainly performed by RNA polymerase II (PolII). POLRMT is responsible for the production of cytoplasmic and nuclear form of mitochondrial RNA polymerase. The former (mtRNAP) participates in transcription of RNA in the mitochondria while the latter (spRNAP-IV) is responsible for some mRNA transcription in the nucleus. The nature and amount of genes transcribed by spRNAP-IV still remains unclear. Thus, we scanned for possible candidate genes by using Affymetrix. MCF7 cells were cultured in RPMI medium supplemented with 10% fetal bovine serum. To determine the inhibition of PolII transcription, cells were cultured in the presence of 10 μg/ml of alpha-amanitin or 0.3μM of triptolide (Sigma) for 48 or 24 h, respectively.
2011-07-01 | E-GEOD-28444 | biostudies-arrayexpress