RBM39 organizes an m⁶A-dependent silencing complex to degrade Tat mRNA and maintain HIV-1 latency
Ontology highlight
ABSTRACT:
INSTRUMENT(S):
ORGANISM(S): Homo Sapiens (human)
TISSUE(S): Cell Culture
SUBMITTER: 
peiming huang
LAB HEAD: panting lab
PROVIDER: PXD064834 | Pride | 2025-10-31
REPOSITORIES: Pride
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| 1227001-3_10.6-NC.pdResult | Other | |||
| 1227001-3_10.6-NC.raw | Raw | |||
| 1227001-4_10.6-T.pdResult | Other | |||
| 1227001-4_10.6-T.raw | Raw | |||
| checksum.txt | Txt |
Items per page: 5 1 - 5 of 5 |
Similar Datasets
Project description:HIV-1 Tat protein is essential for virus production. RNA-binding proteins that facilitate Tat production may be absent or downregulated in resting CD4+ T-cells, the main reservoir of latent HIV. In this study, we examined the role of Tat RNA-binding proteins on the expression of Tat and control of latent and productive infection.
2021-06-14 | PXD025782 | Pride
Project description:LtRNA-derived stress-induced RNAs (tiRNAs) are a new class of small non-coding RNA that have emerged as important regulators of cellular stress responses. tiRNAs are derived from specific tRNA cleavage by the stress-induced ribonuclease angiogenin (ANG). Loss-of-function mutations in the ANG gene are linked to amyotrophic lateral sclerosis (ALS), and elevated levels of specific tiRNAs were recently identified in ALS patient serum samples. However, the biological role of tiRNA production in neuronal stress responses and neurodegeneration remains largely unknown. Here, we sought to evaluate the genome-wide regulation of neuronal stress responses by tiRNAs. First, we demonstrated that a specific tiRNA, 5’tiRNA Gly-GCC , is upregulated in primary neurons exposed to disease-relevant stresses and in the spinal cord of a TDP-43 mouse model of ALS. We then performed whole-transcript RNA sequencing and label-free mass spectrometry on primary neurons transfected with a synthetic mimic of endogenous 5’tiRNA Gly-GCC to identify its effects on global gene and protein expression. Quantitative proteomics identified more than 200 differentially expressed proteins in the 5’tiRNA Gly-GCC mimic-transfected neurons compared to control, however RNA sequencing did not identify any differentially expressed genes in response to tiRNA transfection. Functional enrichment analysis of the proteomic data revealed downregulation of proteins involved in translation initiation, RNA and protein metabolism and also enrichment of pathways associated with several neurodegenerative diseases, including ALS. Together, these findings suggest that 5’tiRNA Gly-GCC is an ALS-associated tiRNA that functions
2024-12-28 | PXD046961 | Pride
Project description:As one of the most common maternal comorbidities, gestational diabetes mellitus (GDM) and preeclampsia (PE) are associated with maternal and infant health. Although the pathogenesis of PE and GDM remains controversial, oxidative stress is thought to be involved in the underlying pathology of GDM and PE. Protein lysine acetylation (Kac) plays an important regulatory role in biological processes. There is little data regarding the association of the maternal acetylome with GDM and PE. This study aimed to assess the multi-omics (proteome and acetylome) potential value in the underlying pathology for GDM and PE by label-free quantification proteomics technology. In our study, we included placental tissue from healthy individuals (n=6), GDM patients (n=6), and PE patients (n=6). We identified 22 overlapping DEPs (differentially expressed proteins) and 192 overlapping DAPs (differentially acetylated proteins) between the GDM and PE groups. Furthermore, 192 overlapping DAPs were mainly enriched in endoplasmic reticulum stress and ferroptosis pathways. Interestingly, endoplasmic reticulum stress, ferroptosis, and oxidative stress are believed to be related to each other. We also identified that acetylation of the HSP90AA1, HSPA8, PDIA3, GPX4, TF, and CP might serve as novel markers and better therapeutic targets in both complications. We thoroughly analyzed the key characteristics of proteome and acetylome in GDM and PE placental tissues, which may be useful for exploring the underlying pathology and discovering new biomarkers and therapeutic targets.
2024-01-25 | PXD032981 | Pride
Project description:We sought to test whether vaccine-induced immune responses could protect rhesus macaques (RMs) against upfront heterologous challenges with an R5 simian-human immunodeficiency virus, SHIV-2873Nip. We immunized the RMs with recombinant Env proteins heterologous to the challenge virus. For induction of immune responses against Gag, Tat, and Nef, we explored a strategy of immunization with overlapping synthetic peptides (OSP). The immune responses against Gag and Tat were finally boosted with recombinant proteins. The vaccinees and a group of ten control animals were given five low-dose intrarectal (i.r.) challenges with SHIV-2873Nip. All controls and seven out of eight vaccinees became systemically infected; there was no significant difference in viremia levels of vaccinees vs. controls. Prevention of viremia was observed in one vaccinee which showed strong boosting of virus-specific cellular immunity during virus exposures. The protected animal showed no challenge virus-specific neutralizing antibodies in the TZM-bl or A3R5 cell-based assays and had low level ADCC activity after the virus exposures. Microarray data strongly supported a role for cellular immunity in the protected animal. Our study represents a case of protection against heterologous tier 2 SHIV-C by vaccine-induced, virus-specific cellular immune responses. For the protected RM, blood was collected before vaccination, on the day of first virus exposure and six weeks after last virus challenge. Lymph node and rectal pinch biopsies were performed before vaccination and six weeks after last virus challenge. Blood was collected in tempus tubes and processed immediately according to the manufacturer’s instructions and stored at -80C. The biopsy specimens were cut into small pieces and immediately placed into RNAlater solution (Qiagen, Valencia, CA) and also stored at -80C. Total RNA from blood, lymph node and rectal biopsies was extracted using RNAeasy extraction kits (Qiagen, Valencia, CA). cDNA labeling, hybridization, staining and scanning were performed according to the manufacturer’s instructions (Affymetrix, Santa Clara, CA) for rhesus gene expression arrays.
2014-08-14 | E-GEOD-60368 | biostudies-arrayexpress
Project description:Recent studies have revealed the importance of long noncoding RNAs (lncRNAs) as tissue-specific regulators of gene expression. There is ample evidence that distinct types of vasculature undergo tight transcriptional control to preserve their structure, identity, and functions. We determined, for the first time, the global lineage-specific lncRNAome of human dermal blood and lymphatic endothelial cells (BECs and LECs), combining RNA-Seq and CAGE-Seq. A subsequent genome-wide antisense oligonucleotide-knockdown profiling of two BEC- and two LEC-specific lncRNAs identified LETR1 as a critical gatekeeper of the global LEC transcriptome. Deep RNA-DNA and RNA-protein interaction studies, and phenotype rescue analyses revealed that LETR1 is a nuclear trans-acting lncRNA modulating, via key epigenetic factors, the expression of essential target genes governing the growth and migratory ability of LECs. Together, our study provides new evidence supporting the intriguing concept that every cell type expresses precise lncRNA signatures to control lineage-specific regulatory programs.
2020-12-21 | PXD018578 | Pride
Project description:We have used RNA immunoprecipitation to identify the set of mRNAs that HIV-1 Tat interacts with in T-cells. We have also performed measurements of relative RNA abundance to determine if Tat binding is associated with an increase in RNA abundance in Tat-expressing T-cells and during HIV infection of primary T-cells. We have also used RNA IP and ChIP-Chip to compare the RNAs with which Tat interacts with to the RNAs that RISC interacts with and the genes associated with pTEF-b.
2013-11-05 | E-MEXP-3199 | biostudies-arrayexpress
Project description:We constructed B cell lines with inducible and stable HIV-1 Tat expression and performed RNA sequencing to study the acute and chronic effects of Tat protein.
2024-05-24 | GSE233499 | GEO
Project description:HIV-1 Tat induces the expression of interferon (IFN)-inducible genes in immature dendritic cells (iDC) in the absence of IFN production. We evaluated how three alleles of Tat and some Tat mutants differ in cellular gene modulation and whether a similar gene induction pattern could be detected by treating cells with IFNM-bM-^@M-^Ys. The three alleles and mutants, with the exception of mutants TatSF21-47 and TatSF2G48-R57A that do not localize in the nucleous, modulated to different degrees IFN-inducible genes without concomitant induction of IFNM-bM-^@M-^Ys. The first exon TatSF21-72 and the minimal transactivator TatSF21-58, all induced genes to a significantly greater extent than full-length Tat. The 2nd exon appears to diminish the gene modulation that can be observed when the first exon alone is expressed. To investigate what domain of Tat are critical to the host-pathogen interactions that are Tat-dependent during HIV infection, we evaluated a variety of Tat-mutants and found that in antigen presenting cells, blood-derived myeloid iDC and macrophages, the second exon of Tat reduces innate immunological responses which are maximal when a Single exon Tat is expressed. 1X10e6 macrophages were infected with HIVBal (20 ng of p24/ 106 cells) for 10 days and with adenoviruses expressing TatHXB2 or LacZ control (5 pfu per cell). Cells infected with Ad-Tat or Ad-LacZ were collected at 24 hours and cells infected with HIV or treated with medium were harvested at 7d and 10d post-infection. THP-Mac were infected with Ad-Tat or Ad-tTA control for 24 hours. RNA was isolated and mRNA expression levels were analyzed by microarrays. adenovirus expressing HIV Tat for 30 hours. and then RNA was isolated, labeled, and prepared for hybridization on Affymetrix microarrays.
2013-06-01 | E-GEOD-42925 | biostudies-arrayexpress
Project description:In children, focal segmental glomerulosclerosis (FSGS) is the main cause of steroid resistant nephroticsyndrome (SRNS). To identify specific candidates and the mechanism of steroid resistance, we examined the formalin-fixed paraffin embedded (FFPE) renal tissue protein profiles via liquid chromatography tandem mass spectrometry (LC-MS/MS). Renal biopsies from seven steroid-sensitive (SS) and eleven steroid-resistant (SR) children FSGS patients were obtained. We examined the formalin-fixed paraffin embedded (FFPE) renal tissue protein profiles via liquid chromatography tandem mass spectrometry (LC-MS/MS). Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and Gene Ontology (GO) analysis, as well as the construction of protein-protein interaction (PPI) network were performed. Two proteins were further valiadated by immunohistochemistry staining in FSGS patients and mice models. In total, we quantified 4794 proteins, of which 325 were found to be differentially expressed proteins (DEPs) between the SS and SR group (foldchange ≥ 2, P＜0.05). The results of GO revealed that the most significant up-regulated proteins were primarily related to protein transportation, regulation of the complement activation process and cytolysis. Moreover, clustering analysis showed differences in the pathways (lysosome, terminal pathway of complement) between the two groups. Among these potential candidates, validation analyses for LAMP1 and ACSL4 were conducted. LAMP1 was observed to have a higher expression in glomerulus, while ACSL4 was expressed more in tubular epithelial cells.
2022-11-19 | PXD036164 | Pride
Project description:The Twin-arginine translocation (Tat) system promotes secretion of folded proteins that in bacteria are identified via an N-terminal signal peptide. Tat systems are associated with virulence in many bacterial pathogens and our previous studies revealed that Tat deficient Yersinia pseudotuberculosis was severely attenuated for virulence. However, in silico predictions did not reveal any obvious virulence factors among the potential Tat substrates encoded by Y. pseudotuberculosis. Aiming to identify Tat dependent pathways and phenotypes of relevance for in vivo infection, we analysed the global transcriptome of parental and â??tatC mutant strains of Y. pseudotuberculosis during exponential and stationary growth at 26°C and 37°C. The most significant changes in the transcriptome of the â??tatC mutant were seen at 26°C during stationary phase growth and these included the altered expression of genes related to virulence, stress responses and metabolism. Subsequent phenotypic analysis based on these transcriptome changes revealed several novel Tat dependent phenotypes including decreased YadA expression, impaired growth under iron-limiting and high copper concentrations as well as sensitivity to acidic pH and SDS. Several functionally related Tat substrates were also verified to contribute to these phenotypes. Interestingly, the phenotypes of the Tat deficient strain were generally more pronounced than for the individual mutants of the genes encoding the specific Tat substrates. Altogether, this provides new insight into the impact of Tat deficiency on in vivo fitness and survival/replication of Y. pseudotuberculosis during infection. Y. pseudotuberculosis IP32953 was grown at 26°C in LB medium under aeration on a rotary shaker. Total RNA was extracted using SV Total RNA Isolation System (Promega). The samples were treated with RNase-free DNase (Roche Applied Science) and the quality of the RNA was confirmed by the lack of PCR amplification of the hns gene and by using an Agilent 2100 Bioanalyzer.
2016-07-01 | E-GEOD-80528 | biostudies-arrayexpress