Hepatitis C virus RNA is 5’ flavin adenine dinucleotide (FAD) capped
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA750141 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR18433500.fastq.gz | Fastqsanger.gz | |||
| SRR18433501.fastq.gz | Fastqsanger.gz | |||
| SRR18433502.fastq.gz | Fastqsanger.gz | |||
| SRR18433503.fastq.gz | Fastqsanger.gz | |||
| SRR18433504.fastq.gz | Fastqsanger.gz |
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Project description:RNA viruses have developed elaborate strategies for 5’ capping and protection of their genomes. However, so far no 5’ RNA cap has been identified for Hepatitis C virus (HCV), which cause chronic infection, liver cirrhosis and cancer in humans4. Here, we demonstrate that the cellular metabolite flavin adenine dinucleotide (FAD) is used as noncanonical initiating nucleotide by the viral RNA-dependent RNA polymerase resulting in a 5’ FAD cap on the HCV RNA. FAD capping is completely conserved for the HCV replication intermediate negative RNA strand and partially for the positive RNA strand. The prototype strain J6/JFH1 RNA is FAD capped when isolated from the liver and serum of a human liver chimeric mouse model and in vitro the FAD capping frequency is ~75 %, which is the highest metabolite RNA capping frequency observed. Furthermore, we show that 5’ FAD capping protects RNA from cell-intrinsic innate immune recognition but has limited effect on HCV RNA stability. These results establish capping with cellular metabolites, such as FAD, as a novel viral RNA capping and immune evasion strategy, which potentially could be used by many viruses for protection of their intermediate RNA strands and thereby affect viral treatment outcomes and persistency.
2022-07-31 | GSE180956 | GEO
Project description:We explored the interactome of flavin adenine dinucleotide (FAD) and the matrix of UV-immobilised FAD bound more than 3,000 proteins from SW-620 lysate. GO enrichment analysis showed that about 600 RNA-binding proteins were bound to FAD beads and, surprisingly, more than 40 proteins showed clear dose-dependent binding competition with nanomolar affinities indicating that their direct or indirect interaction with free FAD is both specific and strong. Among the few known consensus sequences for RNA-binding proteins, we selected the PUF motif 5'-UGUANAUA-3' to investigate whether FAD is binding the Pumilio homologs PUM1 and PUM2 in their RNA-binding pocket, as both these proteins showed dose-response behaviour in the FAD versus FAD-beads. Immobilisation of an oligomer containing the consensus sequence on NHS-activated Sepharose beads yielded PUM-beads that did enrich the Pumilio homologs. Oligomer vs FAD-beads and FAD vs PUM-beads together with the FAD vs FAD-beads dose-response competition indicated that the binding of FAD does not seem to influence the binding of the RNA. It is therefore most likely that FAD binding is allosteric for PUMs.
2022-10-06 | PXD036953 | Pride
Project description:Exposure to environmental stress has a clinically established influence on male reproductive health, but the impact of normal cellular metabolism on sperm quality and function is less well-defined. Here we show that homeostatic changes in mitochondrial dynamics driven by defective mitochondrial proline catabolism result in pleiotropic consequences on sperm quality and competitive fitness. Disruption of alh-6, which converts 1-pyrroline-5-carboxylate (P5C) to glutamate, results in P5C accumulation that drives oxidative stress, activation of the cytoprotective transcription factor SKN-1, and a reduction of energy-storing flavin adenine dinucleotide (FAD) levels. These molecular changes lead to premature male reproductive senescence by reducing sperm quality. These sperm-specific defects are suppressed by abating P5C metabolism, by treatment with antioxidants to combat reactive oxygen species (ROS), or by feeding diets that restore FAD levels. Our results define a role for mitochondrial proline catabolism and FAD homeostasis on sperm function and specify strategies to pharmacologically reverse unintended outcomes from SKN-1/Nrf transcriptional activation.
2020-02-17 | GSE121920 | GEO
Project description:Riboflavin (RF) and its cofactors (FMN and FAD) are essential molecules for vital metabolic processes in all organisms. Thus, the flavin metabolism must be tightly regulated in the cells. We previously demonstrated that the intracellular levels of flavins were tightly maintained by the enzymes involved in their synthesis and degradation, inducing a plastidic FAD hydrolase (AtNUDX23), in Arabidopsis. However, information of regulatory factors involved in the flavin homeostasis and transporters in each organelle are mostly limited. Terefore, we tried to identify novel factors involved in the flavin metabolism, such as transcription factors and transporters by a transcriptome analysis after exogenous FAD treatment.
2021-03-18 | GSE169061 | GEO
Project description:Investigation of transcriptome changes in four human cell lines (BJ, BJ-5ta, U2OS and HeLa) after treatment for 24 hours with nicotinamide adenine dinucleotide (NAD+). Cells were untreated as the control condition. Nanopore sequencing of cDNA was performed after library preparation with the ONT SQK-PCB109 kit.
2023-09-20 | E-MTAB-13187 | biostudies-arrayexpress
Project description:The hub metabolite, nicotinamide adenine dinucleotide (NAD), can be used as an initiating nucleotide in RNA synthesis to result in NAD-capped RNAs (NAD-RNA). We investigated the dynamics of NAD-modified epitranscriptome during human normal aging.
2023-12-20 | GSE226636 | GEO
Project description:Adipogenic differentiation and metabolic adaptation are initiated through transcriptional and epigenetic reprogramming. In particular, dynamic changes in histone modifications may play central roles in the rearrangement of gene expression patterns. LSD1 (KDM1) protein, encoded by aof2 gene, is a histone demethylase, which is involved in transcriptional regulation. Since the enzymatic activity of LSD1 is FAD (flavin adenine dinucleotide)-dependent, its effects on gene expression may be influenced by FAD availability. To address the importance of histone demethylation in adipogenic differentiation and function, we performed cDNA microarray in LSD1-deficient 3T3-L1 cells as well as in the cells treated with LSD1 inhibitor tranylcypromine (TC). FAD-synthesizing enyme, riboflavin kinase (RFK) -deficient cells were also subjected to the microarray analysis. 3T3-L1 preadipocytes were transfected with aof2- or rfk- specific siRNA or control siRNA (siGL3) . 24 hours later, cells were subjected to adipogenic induction. 24 hours later, cells were harvested for total RNA extraction. For the TC treatment, TC was added to the adipogenic induction medium.
2012-04-04 | E-GEOD-18598 | biostudies-arrayexpress
Project description:Adipogenic differentiation and metabolic adaptation are initiated through transcriptional and epigenetic reprogramming. In particular, dynamic changes in histone modifications may play central roles in the rearrangement of gene expression patterns. LSD1 (KDM1) protein, encoded by aof2 gene, is a histone demethylase, which is involved in transcriptional regulation. Since the enzymatic activity of LSD1 is FAD (flavin adenine dinucleotide)-dependent, its effects on gene expression may be influenced by FAD availability. To address the importance of histone demethylation in adipogenic differentiation and function, we performed cDNA microarray in LSD1-deficient 3T3-L1 cells as well as in the cells treated with LSD1 inhibitor tranylcypromine (TC). FAD-synthesizing enyme, riboflavin kinase (RFK) -deficient cells were also subjected to the microarray analysis.
2012-04-05 | GSE18598 | GEO
Project description:The hub metabolite, nicotinamide adenine dinucleotide (NAD), can be used as an initiating nucleotide in RNA synthesis to result in NAD-capped RNAs (NAD-RNA). Since NAD has been heightened as one of the most essential modulators in aging and various age-related diseases, its attachment to RNA might indicate a yet-to-be discovered mechanism that impacts adult life-course. However, the unknown identity of NAD-linked RNAs in adult and aging tissues has hindered functional studies. Here, we introduce ONE-seq method to identify the RNA transcripts that contain NAD cap. ONE-seq has been optimized to use only one-step chemo-enzymatic biotinylation, followed by streptavidin capture and the nudix phosphohydrolase NudC-catalyzed elution, to specifically recover NAD-capped RNAs for epitranscriptome and gene-specific analyses. Our data describes more than a thousand of previously unknown NAD-RNAs in the mouse liver and reveals epitranscriptome-wide dynamics of NAD-RNAs with age.ONE-seq empowers the identification of NAD-capped RNAs that are responsive to distinct physiological states, facilitating functional investigation into this modification.
2022-01-27 | GSE194271 | GEO
Project description:Flavin adenine dinucleotide (FAD) mediates oxidation-reduction reactions required for cellular energy demands. Fatty acid oxidation (FAO) disorders caused by flavoprotein mutations and FAD depletion disrupt energy balance and glucose production during fasting. These FAO disorders are difficult to manage clinically, and their biochemical pathogenesis is poorly understood. Here, we identify a mechanistic connection between FAD levels and hepatic glucose production. Depleting the FAD pool in mice with a vitamin B2 deficient diet (B2D) resulted in phenotypes associated with organic acidemia phenotypes, including reduced body weight and whole-body fat oxidation rates coupled with hypoglycemia. Integrated discovery approaches revealed that B2D broadly tempered fasting activation of target genes for the nuclear receptor PPARa, including those required for gluconeogenesis. Consistent with this, Ppara knockout depleted liver FAD levels and worsened B2D hepatic glucose production. Treatment with the PPARa agonist fenofibrate overcame B2D phenotypes and rescued glucose availability and fatty liver signatures through activation of the integrated stress response and refilling anaplerotic amino acid substrates for glucose production. We conclude that PPARa governs metabolic responses to FAD availability and suggest pharmacologic activation as a strategy for treating disorders of riboflavin and FAD deficiency.
2022-06-18 | GSE206200 | GEO