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ATM, KAP1 and the Epstein-Barr virus polymerase processivity factor direct traffic at the intersection of transcription and replication.

The timing of transcription and replication must be carefully regulated for heavily-transcribed genomes of double-stranded DNA viruses: tran … AP1's SUMO2-ligase function is triggered by phosphorylation via the PI3K-related kinase ATM and the RNA polymerase II-associated helicase RECQ5 at the transcription machinery. SUMO2-EA-D then recruits the histone loader CAF1 and the methyltransferase SETDB1 to silence the parental genome via H3K9 methylation, prioritizing replication. Thus, a key viral protein and …

Leishmania spp. identification by polymerase chain reaction-restriction fragment length polymorphism analysis and its applications in French Guiana.

Leishmania (Viannia) guyanensis was for many years the only species commonly identified in French Guiana, but precise species identifications were quite rare. We describe a new restriction fragment length polymorphism-polymerase chain reaction technique using a 615-bp fragment of the RNA polymerase II gene and 2 restriction enzymes, TspRI and HgaI. Seven reference strains (Leishmania (Leishmania) amazonensis, Leishmania (Viannia) lainsoni, Leishmania (Viannia) braziliensis, L. (V.) guyanensis, Leishmania (Viannia) naiffi, Leishmania (Leishmania) major, Leishmania (Leishmania) infantum) and 112…

Transcriptional activity during seed imbibition is conserved, robust and required for germination.

In most plants, germination begins with the reactivation of metabolism during water uptake by the desiccated seed. Notably, Pol II transcription is hypothesised not to be required for early germination, as seeds appear to initially rely on stored mRNAs produced during their maturation. Here, we show that efficient blocking of Pol II transcription completely stops germination in Arabidopsis seeds. Pol II activity is initiated early and is widespread, following expression and Pol II binding patterns established during seed drying. Our findings suggest that the earliest transcriptional phase reli

The Plasmodium falciparum Nuclear Protein Phosphatase NIF4 Is Required for Efficient Merozoite Invasion and Regulates Artemisinin Sensitivity.

Artemisinin resistance in Plasmodium falciparum has been associated with a mutation in the NLI-interacting factor-like phosphatase PfNIF4, i … bserved increased phosphorylation of Ser2/5 of the tandem repeats in the C-terminal domain (CTD) of RNA polymerase II (RNAPII) upon PfNIF4 KD. Furthermore, using the TurboID-based proteomic approach, we identified that PfNIF4 interacted with the RNAPII components, AP2-domain transcription factors, and chromatin-modifiers and binders. These findings suggest that PfN …

Hepatitis C virus (HCV) in lymphocyte subsets and in B lymphocytes expressing rheumatoid factor cross-reacting idiotype in type II mixed cryoglobulinaemia.

The IgMk rheumatoid factors (RF) of type II mixed cryoglobulinaemia (MC) react, in 95% of cases, with MoAbs against the cross-reactive idiotypes (CRI) Cc1 or Lc1 (corresponding to the products of the VH1 and VH4 genes). MC is closely associated with HCV infection, a virus which infects lymphocytes and may replicate in B cells. It has been suggested that HCV may induce clonal selection of B cells producing monoclonal IgMk RF in type II MC. To verify whether HCV is enriched in B cells, and in the subsets expressing Cc1 and Lc1 CRI, we studied peripheral blood lymphocytes from eight patients with

Adenovirus type 12-induced fragility of the human RNU2 locus requires p53 function.

Adenovirus type 12 (Ad12) infection of human cells induces four chromosomal fragile sites corresponding to the U1 small nuclear RNA (snRNA) … sforming protein (and possibly E4orf6) induces a p53 gain of function which ultimately perturbs the RNA polymerase II basal transcription apparatus. The p53 gain of function could interfere with chromatin condensation either by blocking mitotic shutdown of U1 and U2 snRNA transcription or by phenocopying global or local DNA damage. Specific fragilization of the RNU …

Cyclin dependent kinase 9 inhibitor induces transcription-replication conflicts and DNA damage accumulation in breast cancer.

BACKGROUND: Cyclin-dependent kinase 9 (CDK9) is a crucial regulator of transcriptional progression of RNA polymerase-II (RNAP2). RNA polymerases trapped in DNA can be a source of transcription-replication conflict (T-R conflict), which is a common source of replication stress. AZD4573, a highly selective CDK9 inhibitor, has been shown to induce apoptosis in leukemia cell lines, while its anti-tumor potential in breast cancer has yet to be elucidated. METHODS: To evaluate the cytotoxicity of AZD4573 in vitro, MTT assays were performed. The expression of signal transduction molecules was determ

Class II HLA associations with autoantibodies in scleroderma: a highly significant role for HLA-DP.

Scleroderma is a condition of variable phenotype characterised by fibrosis of the skin and internal organs. There is a range of disease-specific autoantibodies found in the sera of patients. The aims of this study were to: (1) investigate the role of the MHC and particularly HLA-DP in the production of autoantibodies; (2) investigate clinical associations with autoantibodies. We have performed HLA class II typing using PCR with sequence-specific primers on DNA samples from 202 scleroderma patients and 307 UK control subjects. All patients had well defined clinical phenotypes. Sera from patient

Angiotensin II type 1 receptor messenger RNA levels in human blood cells of patients with primary and secondary hypertension: reference to renin profile.

OBJECTIVES: The relationship between plasma renin activity, plasma angiotensin II (Ang II) or aldosterone levels and peripheral blood cells (mononuclear leucocytes and platelets) Ang II type 1 (AT1) receptor messenger RNA (mRNA) levels were examined in both primary and secondary hypertensive patients. DESIGN AND METHODS: The subjects were 30 patients with primary hypertension, five with primary aldosteronism, five with renovascular hypertension and five normotensive controls with renal cell carcinoma. Blood was collected from each patient for estimation of plasma renin activity and plasma Ang

Azilsartan ameliorates ventricular hypertrophy in rats suffering from pressure overload-induced cardiac hypertrophy by activating the Keap1-Nrf2 signalling pathway.

OBJECTIVES: Investigate if azilsartan protects against myocardial hypertrophy by upregulating nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated pathways. METHODS: Abdominal aortic constriction (AAC)-induced cardiac hypertrophy in rats was applied. Azilsartan or vehicle was administered daily for 6 weeks in sham or AAC rats. Cardiac morphology and ventricular function were determined. Azilsartan effects upon neonatal rat cardiomyocyte (NRCM) hypertrophy and molecular mechanisms were studied in angiotensin (Ang) II-stimulated NRCMs in vitro. Nrf2-small interfering RNA (siRNA) was used

Indirubin-3'-monoxime обладает мощными антивирусными и противовоспалительными эффектами против аденовирусов человека in vitro и in vivo.

Инфекция аденовируса человека (HAdV) является одной из основных причин респираторных заболеваний, однако для ее лечения не было принято никаких антивирусных препаратов. Здесь мы провели оценку антивирусного и противовоспалительного воздействия ингибитора белковой киназы (CDK) ингибитора indirubin-3'-monoxime (IM) на инфекцию HADV в клетках и трансгенную модель мыши. После оценки цитотоксичности, уменьшения цитопатического эффекта, репликации антивирусных кинетик, а также анализа на снижение урожайности вирусов для оценки антиHAdV-активности IM. Количественная цепная реакция полимеразы в режиме

Совпадение в аннотации оригинала
Human adenovirus (HAdV) infection is a major cause of respiratory disease, yet no antiviral drugs have been approved for its treatment. Here … as E1A and Hexon transcription, in addition to significantly suppressing the phosphorylation of the RNA polymerase II C-terminal domain (CTD). IM mitigated body weight loss, reduced viral burden, and lung injury, decreasing cytokine and chemokine secretion to a greater extent than cidofovir. Altogether, IM inhibits HAdV replication by downregulating CTD phosphoryla …

Expression of angiotensin II and its receptors in cyclosporine-induced gingival overgrowth.

BACKGROUND AND OBJECTIVES: The renin-angiotensin system (RAS) is considered as a hormonal circulatory system involved in maintaining blood pressure, electrolyte and fluid homeostasis. RAS components can be synthesized in local tissues and are found to play a role in gingival overgrowth. The drug-induced gingival overgrowth (DIGO) is a fibrotic condition, which is associated with multiple factors, including inflammation and adverse drug effects such as cyclosporine A. This study was directed forward to the identification of the angiotensinogen, angiotensin II (Ang II) and its receptors AT₁ /AT₂

Characterization of Toxoplasma gondii Spt5 like transcription elongation factor.

Elongation has emerged as a highly regulated step in the multistage process of transcription. Control of gene expression mediated through transcription elongation remains an unexplored area of study in Toxoplasma gondii where the demands of complex lifecycle necessitate a regulated transcription program. Here, we elucidate the central role of Spt5 homolog in T. gondii mRNA transcription. We demonstrate that TgSpt5 functions in conjunction with a small zinc finger protein TgSpt4. TgSpt5 interacts with TgRpb1, the largest subunit of RNA polymerase II and associates with actively transcribed gene…

Chemical perturbation of an intrinsically disordered region of TFIID distinguishes two modes of transcription initiation.

Intrinsically disordered proteins/regions (IDPs/IDRs) are proteins or peptide segments that fail to form stable 3-dimensional structures in the absence of partner proteins. They are abundant in eukaryotic proteomes and are often associated with human diseases, but their biological functions have been elusive to study. In this study, we report the identification of a tin(IV) oxochloride-derived cluster that binds an evolutionarily conserved IDR within the metazoan TFIID transcription complex. Binding arrests an isomerization of promoter-bound TFIID that is required for the engagement of Pol II

Distribution and predominance of genotype 3 in hepatitis C virus carriers in the province of kahramanmaras, Turkey.

BACKGROUND: The hepatitis C virus (HCV) has six major genotypes and more than 100 subtypes, and the determination of the responsible genotype, collection of epidemiological data, tailoring antiviral therapy, and prediction of prognosis have an important place in disease management. OBJECTIVES: The aim of the present study was to determine the distribution of HCV genotypes across geographic regions and compare these data with those obtained from other geographic locations. PATIENTS AND METHODS: The HCV genotypes were identified in HCV RNA positive blood samples, obtained from different center

Discovery of non-nucleoside inhibitors of the enterovirus D68 3D polymerase through crystallographic fragment and high-throughput biochemical screening.

Enterovirus D68 (EV-D68) is a non-polio picornavirus that has caused increasing rates of severe respiratory illness and acute flaccid myelitis in children worldwide this century. There are no approved vaccines or antivirals for EV-D68. Thus, we conducted a crystallographic fragment screening (CFS) and a high-throughput screening (HTS) biochemical assay against the EV-D68 RNA-dependent RNA polymerase 3D (3D pol ) to identify ligandable sites and non-nucleoside compounds that can spearhead anti-enteroviral drug discovery. The CFS, involving 650 fragments, identified 68 hit compounds (~10% hit ra

Upregulation of the Na(+)-K(+)-2Cl(-) cotransporter 1 via histone modification in the aortas of angiotensin II-induced hypertensive rats.

The Na(+)-K(+)-2Cl(-) cotransporter 1 (NKCC1) is upregulated in diverse models of hypertension. We hypothesized that NKCC1 is upregulated vi … 27me3), a repressive histone code, was greatly decreased in Ang II-infused rats compared with sham. RNA polymerase II was recruited to the Nkcc1 promoter with increased KDM6b. We conclude that the NKCC1 is upregulated via histone modification in the aortas of Ang II-induced hypertensive rats. Thus, we suggest that this ion transporter is epigenetically upregulated …

EWS/Fli-1 chimeric protein is a transcriptional activator.

Fli-1, an ets related gene, was found to be rearranged in 75% of erythroleukemias induced by Friend murine leukemia virus. We have shown pre … f Fli-1 was replaced with the amino terminal domain of the EWS (NTD-EWS) which shares homology with RNA polymerase II, it was speculated that NTD-EWS may interfere with RNA pol II function. Alternatively, NTD-EWS could also contribute to the transcriptional activation function of EWS/Fli-1 chimeric protein by providing either a modulatory/regulatory domain or a nov …

Splice-site pairing is an intrinsically high fidelity process.

The extensive alternative splicing in higher eukaryotes has initiated a debate whether alternative mRNA isoforms are generated by an inaccurate spliceosome or are the consequence of highly degenerate splice sites within the human genome. Here, we established a quantitative assay to evaluate the accuracy of splice-site pairing by determining the number of incorrect exon-skipping events made from constitutively spliced pre-mRNA transcripts. We demonstrate that the spliceosome pairs exons with an astonishingly high degree of accuracy that may be limited by the quality of pre-mRNAs generated by RN