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Dinucleotide regulation by REXO2 maintains promoter specificity in mammalian mitochondria

ABSTRACT: Dinucleotide regulation by REXO2 maintains promoter specificity in mammalian mitochondria

PROVIDER: PRJNA532544 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8887360_1.fastq.gz	Fastqsanger.gz
	SRR8887360_2.fastq.gz	Fastqsanger.gz
	SRR8887361_1.fastq.gz	Fastqsanger.gz
	SRR8887361_2.fastq.gz	Fastqsanger.gz
	SRR8887362_1.fastq.gz	Fastqsanger.gz

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Dinucleotide regulation by REXO2 maintains promoter specificity in mammalian mitochondria

Project description:Oligoribonucleases are conserved enzymes that degrade short RNA molecules of up to 5 nt in length, and are assumed to constitute the final stage of RNA turnover. We have investigated the function of the mammalian oligoribonuclease REXO2 through a combination of biochemical, structural and animal model studies. We find that REXO2 is a specialised dinucleotide degrading enzyme that shows no preference between RNA and DNA dinucleotide substrates. This specialisation is explained by crystal structures of REXO2 bound to RNA or DNA substrates. REXO2 is an essential gene, while a heart and skeletal muscle-specific knockout mouse displays elevated dinucleotide levels and alterations in gene expression patterns indicative of aberrant dinucleotide-primed transcription initiation. We find that dinucleotides act as potent stimulators of mitochondrial transcription initiation in vitro, and conclude that efficient RNA turnover is required to maintain the promoter specificity of transcription in mammalian mitochondria.

2019-10-03 | GSE129707 | GEO

Dinucleotide Degradation by REXO2 Maintains Promoter Specificity in Mammalian Mitochondria.

Project description:Oligoribonucleases are conserved enzymes that degrade short RNA molecules of up to 5 nt in length and are assumed to constitute the final stage of RNA turnover. Here we demonstrate that REXO2 is a specialized dinucleotide-degrading enzyme that shows no preference between RNA and DNA dinucleotide substrates. A heart- and skeletal-muscle-specific knockout mouse displays elevated dinucleotide levels and alterations in gene expression patterns indicative of aberrant dinucleotide-primed transcription initiation. We find that dinucleotides act as potent stimulators of mitochondrial transcription initiation in vitro. Our data demonstrate that increased levels of dinucleotides can be used to initiate transcription, leading to an increase in transcription levels from both mitochondrial promoters and other, nonspecific sequence elements in mitochondrial DNA. Efficient RNA turnover by REXO2 is thus required to maintain promoter specificity and proper regulation of transcription in mammalian mitochondria.

| S-EPMC6900737 | biostudies-literature

Cbx3 Maintains Lineage Specificity During Neural Differentiation

Project description:Cbx3 Maintains Lineage Specificity During Neural Differentiation

| PRJNA352606 | ENA

Nicotinamide adenine dinucleotide is transported into mammalian mitochondria.

Project description:Mitochondrial NAD levels influence fuel selection, circadian rhythms, and cell survival under stress. It has alternately been argued that NAD in mammalian mitochondria arises from import of cytosolic nicotinamide (NAM), nicotinamide mononucleotide (NMN), or NAD itself. We provide evidence that murine and human mitochondria take up intact NAD. Isolated mitochondria preparations cannot make NAD from NAM, and while NAD is synthesized from NMN, it does not localize to the mitochondrial matrix or effectively support oxidative phosphorylation. Treating cells with nicotinamide riboside that is isotopically labeled on the nicotinamide and ribose moieties results in the appearance of doubly labeled NAD within mitochondria. Analogous experiments with doubly labeled nicotinic acid riboside (labeling cytosolic NAD without labeling NMN) demonstrate that NAD(H) is the imported species. Our results challenge the long-held view that the mitochondrial inner membrane is impermeable to pyridine nucleotides and suggest the existence of an unrecognized mammalian NAD (or NADH) transporter.

| S-EPMC6013257 | biostudies-literature

Thioredoxin-1 (Trx1) maintains mitochondria function via mTOR signaling in the heart

Project description:Thioredoxin-1 (Trx1) maintains mitochondria function via mTOR signaling in the heart

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Cyclic dinucleotide stimulation of Nematostella vectensis

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Hydroxylation of 5-methylcytosine by TET2 maintains the active state of the mammalian HOXA cluster

Project description:This SuperSeries is composed of the following subset Series: GSE32362: Hydroxylation of 5-methylcytosine by TET2 maintains the active state of the mammalian HOXA cluster (Illumina HumanMethylation450 BeadChip) GSE33129: Hydroxylation of 5-methylcytosine by TET2 maintains the active state of the mammalian HOXA cluster (Illumina HiSeq2000 sequencing) Refer to individual Series

2012-05-02 | E-GEOD-33130 | biostudies-arrayexpress

Transcriptional cofactors display core promoter class-specificity

Project description:Transcriptional cofactors display core promoter class-specificity

| PRJNA477764 | ENA

camelus dromedarius mitochondria

Project description:camelus dromedarius mitochondria

| PRJEB63970 | ENA

Enhancer-core promoter specificity separates developmental and housekeeping regulation

Project description:Gene transcription in animals involves the assembly of the RNA polymerase II complex at core promoters and its cell type-specific activation by genomic enhancers that can be located more distally. However, how ubiquitous expression of housekeeping genes is achieved has remained less clear. In particular, it is unknown whether ubiquitously active enhancers exist and how developmental and housekeeping gene regulation is separated. An attractive hypothesis is that different types of core promoters might exhibit an intrinsic specificity towards certain types of enhancers. Here, we show that thousands of enhancers in D. melanogaster S2 cells and ovarian somatic cells (OSCs) exhibit a marked specificity towards one of two core promoters M-bM-^@M-^S one derived from a ubiquitously expressed ribosomal protein gene and another from a developmentally regulated transcription factor. Enhancers that activate the housekeeping core promoter are functional across the two different cell types, while developmental enhancers exhibit strong cell type specificity. Both enhancer classes differ in their overall genomic distribution, the functions of neighbouring genes,these genesM-bM-^@M-^Y core promoter elements, as well as the associated factors. Our results provide evidence for a sequence-encoded enhancer-core promoter specificity that separates developmental and housekeeping gene regulatory programs for thousands of enhancers and their target genes across the entire genome. STARR-seq was performed in S2 and OSC cells using two core promoters each representing housekeeping and developmental transcription programs. Data for housekeeping promoters (hkCP) are presented in this series; Data for developmental core promoters (dCP) samples are presented in GSE40739.

2014-12-10 | E-GEOD-57876 | biostudies-arrayexpress

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