Tyrosine-1 of RNA Polymerase II CTD Controls Global Termination of Gene Transcription in Mammals.

The carboxy-terminal domain (CTD) of RNA polymerase (Pol) II is composed of a repetition of YSPTSPS heptads and functions as a loading platform for protein complexes that regulate transcription, splicing, and maturation of RNAs. Here, we studied mammalian CTD mutants to analyze the function of tyrosine1 residues in the transcription cycle. Mutation of 3/4 of the tyrosine residues (YFFF mutant) resulted in a massive read-through transcription phenotype in the antisense direction of promoters as well as in the 3' direction several hundred kilobases downstream of genes. The YFFF mutant shows reduced Pol II at promoter-proximal pause sites, a loss of interaction with the Mediator and Integrator complexes, and impaired recruitment of these complexes to chromatin. Consistent with these observations, Pol II loading at enhancers and maturation of snRNAs are altered in the YFFF context genome-wide. We conclude that tyrosine1 residues of the CTD control termination of transcription by Pol II.

Dynamics of broad H3K4me3 domains uncover an epigenetic switch between cell identity and cancer-related genes.

Broad domains of H3K4 methylation have been associated with consistent expression of tissue-specific, cell identity, and tumor suppressor genes. Here, we identified broad domain-associated genes in healthy human thymic T cell populations and a collection of T cell acute lymphoblastic leukemia (T-ALL) primary samples and cell lines. We found that broad domains are highly dynamic throughout T cell differentiation, and their varying breadth allows the distinction between normal and neoplastic cells. Although broad domains preferentially associate with cell identity and tumor suppressor genes in normal thymocytes, they flag key oncogenes in T-ALL samples. Moreover, the expression of broad domain-associated genes, both coding and noncoding, is frequently deregulated in T-ALL. Using two distinct leukemic models, we showed that the ectopic expression of T-ALL oncogenic transcription factor preferentially impacts the expression of broad domain-associated genes in preleukemic cells. Finally, an H3K4me3 demethylase inhibitor differentially targets T-ALL cell lines depending on the extent and number of broad domains. Our results show that the regulation of broad H3K4me3 domains is associated with leukemogenesis, and suggest that the presence of these structures might be used for epigenetic prioritization of cancer-relevant genes, including long noncoding RNAs.

Coronary artery complications with left bundle branch area pacing: A review of literature.

Left bundle branch area pacing (LBBAP) is an emerging technique in cardiac resynchronization therapy that shows promise in improving ventricular synchrony and clinical outcomes in patients with heart failure. However, the potential risk of coronary artery complications with LBBAP necessitates careful attention and management. This literature review explores the mechanisms, acute coronary events, and clinical implications associated with coronary artery complications in LBBAP. The mechanism of coronary injury with LBBAP involves mechanical trauma, altered coronary blood flow dynamics, and endothelial damage. Acute coronary events such as myocardial ischemia, acute coronary syndromes, and coronary artery dissection can occur during or after LBBAP, leading to significant clinical implications including the need for prompt intervention and potential impact on long-term outcomes. To avoid coronary injury and acute coronary syndrome with LBBAP, specific care strategies are recommended. These include thorough pre-procedural evaluation, expert operator technique, optimization of hemodynamics and ventricular synchrony, close monitoring for ischemic events, collaboration with cardiology specialists, and long-term follow-up. The clinical implications of coronary artery complications with LBBAP necessitate careful patient selection, informed decision-making, and a multidisciplinary approach. Future directions in this field include advancements in procedural techniques, technological innovations, risk stratification strategies, enhanced imaging modalities, research on mechanisms and prevention, and collaboration among stakeholders. By implementing these strategies and focusing on future advancements, healthcare providers can minimize the risk of coronary artery complications with LBBAP and optimize patient outcomes in cardiac resynchronization therapy.

Fra-1 regulates its target genes via binding to remote enhancers without exerting major control on chromatin architecture in triple negative breast cancers.

The ubiquitous family of dimeric transcription factors AP-1 is made up of Fos and Jun family proteins. It has long been thought to operate principally at gene promoters and how it controls transcription is still ill-understood. The Fos family protein Fra-1 is overexpressed in triple negative breast cancers (TNBCs) where it contributes to tumor aggressiveness. To address its transcriptional actions in TNBCs, we combined transcriptomics, ChIP-seqs, machine learning and NG Capture-C. Additionally, we studied its Fos family kin Fra-2 also expressed in TNBCs, albeit much less. Consistently with their pleiotropic effects, Fra-1 and Fra-2 up- and downregulate individually, together or redundantly many genes associated with a wide range of biological processes. Target gene regulation is principally due to binding of Fra-1 and Fra-2 at regulatory elements located distantly from cognate promoters where Fra-1 modulates the recruitment of the transcriptional co-regulator p300/CBP and where differences in AP-1 variant motif recognition can underlie preferential Fra-1- or Fra-2 bindings. Our work also shows no major role for Fra-1 in chromatin architecture control at target gene loci, but suggests collaboration between Fra-1-bound and -unbound enhancers within chromatin hubs sometimes including promoters for other Fra-1-regulated genes. Our work impacts our view of AP-1.

Impact of COVID-19 pandemic on health care workers (HCWs) in Sindh Province of Pakistan.

BACKGROUND: In Pakistan, the COVID-19 outbreak posed a significant challenge for healthcare workers in the country's public hospitals. The HCWs faced several problems in terms of the COVID-19 pandemic. Therefore this study investigated how the COVID-19 pandemic has affected the medical staff at the public hospital in Sindh Province, Pakistan. METHODS: In this study, a qualitative exploratory design was used. Semi-Structure interviews (SSI) were conducted by using an open-indeed questionnaire (OIQ) for data collection. An inductive approach was used for theoretical data analysis. A total of 320 HCWs participated to complete the criteria of the study from 10 different public hospitals. RESULTS: The study result showed the Sindh public hospital's insufficient infrastructure, lack of health protective equipment, shortages of isolation rooms and beds, and emergencies during the COVID-19 pandemic caused HCWs to experience physical and psychological weariness, sleep disturbance, mental stress, and fear of infection. CONCLUSION: The study concluded that public hospitals' insufficient infrastructure, furniture, emergency wards, and safety equipment during the COVID-19 pandemic significantly damaged HCWs' physical and psychological health, generating fear of infection and sleep disturbance. Additionally, Sindh healthcare workers' fear of illness and isolation may impair family connections.

Entropy Related to K-Banhatti Indices via Valency Based on the Presence of C6H6 in Various Molecules.

Entropy is a measure of a system's molecular disorder or unpredictability since work is produced by organized molecular motion. Shannon's entropy metric is applied to represent a random graph's variability. Entropy is a thermodynamic function in physics that, based on the variety of possible configurations for molecules to take, describes the randomness and disorder of molecules in a given system or process. Numerous issues in the fields of mathematics, biology, chemical graph theory, organic and inorganic chemistry, and other disciplines are resolved using distance-based entropy. These applications cover quantifying molecules' chemical and electrical structures, signal processing, structural investigations on crystals, and molecular ensembles. In this paper, we look at K-Banhatti entropies using K-Banhatti indices for C6H6 embedded in different chemical networks. Our goal is to investigate the valency-based molecular invariants and K-Banhatti entropies for three chemical networks: the circumnaphthalene (CNBn), the honeycomb (HBn), and the pyrene (PYn). In order to reach conclusions, we apply the method of atom-bond partitioning based on valences, which is an application of spectral graph theory. We obtain the precise values of the first K-Banhatti entropy, the second K-Banhatti entropy, the first hyper K-Banhatti entropy, and the second hyper K-Banhatti entropy for the three chemical networks in the main results and conclusion.

Vitamin K: A novel cancer chemosensitizer.

Cancer incidences are growing rapidly and causing millions of deaths globally. Cancer treatment is one of the most exigent challenges. Drug resistance is a natural phenomenon and is considered one of the major obstacles in the successful treatment of cancer by chemotherapy. Combination therapy by the amalgamation of various anticancer drugs has suggested modulating tumor response by targeting various signaling pathways in a synergistic or additive manner. Vitamin K is an essential nutrient and has recently been investigated as a potential anticancer agent. The combination of vitamin K analogs, such as vitamins K1, K2, K3, and K5, with other chemotherapeutic drugs have demonstrated a safe, cost-effective, and most efficient way to overcome drug resistance and improved the outcomes of prevailing chemotherapy. Published reports have shown that vitamin K in combination therapy improved the efficacy of clinical drugs by promoting apoptosis and cell cycle arrest and overcoming drug resistance by inhibiting P-glycoprotein. In this review, we discuss the mechanism, cellular targets, and possible ways to develop vitamin K subtypes into effective cancer chemosensitizers. Finally, this review will provide a scientific basis for exploiting vitamin K as a potential agent to improve the efficacy of chemotherapeutic drugs.

A comprehensive review on anticancer mechanism of bazedoxifene.

Cancer is counted as a second leading cause of death among nontransmissible diseases. Identification of novel anticancer drugs is therefore necessary for the effective treatment of cancer. Conventional drug discovery is time consuming and expensive process. Unlike conventional drug discovery, drug repositioning offers a novel strategy for urgent drug discovery since it is a cost-effective and faster process. Bazedoxifene (BZA) is a synthetic selective estrogen receptor modulator, approved by the United States Food and Drug Administration for the treatment of osteoporosis in postmenopausal women. BZA is now being studied for its anticancer activity in various cancers including breast cancer, liver cancer, pancreatic cancer, colon cancer, head and neck cancer, medulloblastoma, brain cancer, and gastrointestinal cancer. Studies have reported that BZA is effective in reducing cancer progression through multiple mechanisms. BZA could effectively inhibit STAT3, PI3K/AKT, and MAPK signaling pathways and induce apoptosis. In addition to its anticancer activity as monotherapy, BZA has been shown to enhance the chemotherapeutic efficacy of clinical drugs such as paclitaxel, cisplatin, palbociclib, and oxaliplatin in multiple neoplasms. This review mainly focused on the anticancer activity, cellular targets, and anticancer mechanism of BZA, which may help the further design and conduct of research and repositioning it for oncological clinic trials.

In situtailoring the morphology of In(OH)3nanostructures via surfactants during anodization and their transformation into In2O3nanoparticles.

The present work reports the effect of various surfactants on the morphology of In(OH)3nanostructures prepared via anodization. In-sheets were anodized in an environmentally benign electrolyte containing a small quantity of CTAB, CTAC, and PDDA surfactants at room temperature. The produced nanostructures were characterized using XRD, HRTEM, SAED, and EDAX. The morphology of indium hydroxide (In(OH)3) nanostructures was successfully tailoredin situwith the help of surfactants in 1 M KCl aqueous electrolyte. XRD results confirmed the formation of In(OH)3and indium oxyhydroxide (InOOH) nanostructures in the pristine form which were transformed into single-phase cubic In2O3nanoparticles (NPs) after calcination. HRTEM analyses showed that the morphology and size of the In(OH)3nanostructures can be tuned to form nanorods, nanosheets and nanostrips using different surfactants. The results revealed that CTAC and PDDA surfactants have a profound effect on the morphology of In(OH)3nanostructure compared to CTAB due to the higher concentration of Cl-ion. The possible mechanism of surfactants effect on the morphology is proposed. Furthermore, annealing converted the In(OH)3nanostructures into spherical In2O3NPs with uniform and homogeneous size. We anticipate that the morphology of other metal-oxides nanostructure can be tuned using this simple, facile and rapid technique. In2O3NPs prepared without and with CTAB surfactant were further explored for the non-enzymatic detection of hydrogen peroxide (H2O2). Electrochemical measurements showed enhanced electrocatalytic performance with fast electron transfer (∼2s) between the redox centers of H2O2and electrode surface. The In2O3NPs prepared using CTAB/Au electrode exhibited about 4-fold increase in sensitivity compared to the bare Au electrode. The biosensor also demonstrated good reproducibility, higher selectivity, and increased shelf life.

Review on the hazardous applications and photodegradation mechanisms of chlorophenols over different photocatalysts.

Chlorophenols are very important environmental pollutants, which have created huge problems for both aquatic and terrestrial lives. Therefore, their removal needs urgent, effective, and advanced technologies to safeguard our environment for future generation. This review encompasses a comprehensive study of the applications of chlorophenols, their hazardous effects and photocatalytic degradation under light illumination. The effect of various factors such as pH and presence of different anions on the photocatalytic oxidation of chlorophenols have been elaborated comprehensively. The production of different oxidizing agents taking part in the photodegradation of chlorophenols are given a bird eye view. The photocatalytic degradation mechanism of different chlorophenols over various photocatalyts has been discussed in more detail and elaborated that how different photocatalysts degrade the same chlorophenols with the aid of different oxidizing agents produced during photocatalysis. Finally, a future perspective has been given to deal with the effective removal of these hazardous pollutants from the environment.

Cytidine deamination-induced perpetual immunity to SAR-CoV-2 infection is a potential new therapeutic target.

As the world is racing to develop perpetual immunity to the SARS-CoV-2 virus. The emergence of new viral strains, together with vaccination and reinfections, are all contributing to a long-term immunity against the deadly virus that has taken over the world since its introduction to humans in late December 2019. The discovery that more than 95 percent of people who recovered from COVID-19 had long-lasting immunity and that asymptomatic people have a different immune response to SARS-CoV-2 than symptomatic people has shifted attention to how our immune system initiates such diverse responses. These findings have provided reason to believe that SARS-CoV-2 days are numbered. Hundreds of research papers have been published on the causes of long-lasting immune responses and variations in the numbers of different immune cell types in COVID 19 survivors, but the main reason of these differences has still not been adequately identified. In this article, we focus on the activation-induced cytidine deaminase (AID), which initiates molecular processes that allow our immune system to generate antibodies against SARS-CoV-2. To establish lasting immunity to SARS-CoV-2, we suggest that AID could be the key to unlocking it.

MIR sequences recruit zinc finger protein ZNF768 to expressed genes.

Mammalian-wide interspersed repeats (MIRs) are retrotransposed elements of mammalian genomes. Here, we report the specific binding of zinc finger protein ZNF768 to the sequence motif GCTGTGTG (N20) CCTCTCTG in the core region of MIRs. ZNF768 binding is preferentially associated with euchromatin and promoter regions of genes. Binding was observed for genes expressed in a cell type-specific manner in human B cell line Raji and osteosarcoma U2OS cells. Mass spectrometric analysis revealed binding of ZNF768 to Elongator components Elp1, Elp2 and Elp3 and other nuclear factors. The N-terminus of ZNF768 contains a heptad repeat array structurally related to the C-terminal domain (CTD) of RNA polymerase II. This array evolved in placental animals but not marsupials and monotreme species, displays species-specific length variations, and possibly fulfills CTD related functions in gene regulation. We propose that the evolution of MIRs and ZNF768 has extended the repertoire of gene regulatory mechanisms in mammals and that ZNF768 binding is associated with cell type-specific gene expression.

Hispidulin: A novel natural compound with therapeutic potential against human cancers.

Cancer is one of the most devastating disease and leading cause of death worldwide. The conventional anticancer drugs are monotarget, toxic, expensive and suffer from drug resistance. Development of multi-targeted drugs from natural products has emerged as a new paradigm to overcome aforementioned conventionally encountered obstacles. Hispidulin (HIS), is a biologically active natural flavone with versatile biological and pharmacological activities. The anticancer, antimutagenic, antioxidative and anti-inflammatory properties of HIS have been reported. The aim of this review is to summarize the findings of several studies over the last few decades on the anticancer activity of HIS published in various databases including PubMed, Google Scholar, and Scopus. HIS has been shown to reduce the growth of cancer cells by inducing apoptosis, arresting cell cycle, inhibiting angiogenesis, invasion and metastasis via modulating multiple signaling pathways implicated in cancer initiation and progression. Multitargeted anticancer activity of HIS remains the strongest point for developing it into potential anticancer drug. We also highlighted the natural sources, anticancer mechanism, cellular targets, and chemo-sensitizing potential of HIS. This review will provide bases for design and conduct of further pre-clinical and clinical trials to develop HIS into a lead structure for future anticancer therapy.

Synthesis, Characterization, Antibacterial Properties, and In Vitro Studies of Selenium and Strontium Co-Substituted Hydroxyapatite.

In this study, as a measure to enhance the antimicrobial activity of biomaterials, the selenium ions have been substituted into hydroxyapatite (HA) at different concentration levels. To balance the potential cytotoxic effects of selenite ions (SeO32-) in HA, strontium (Sr2+) was co-substituted at the same concentration. Selenium and strontium-substituted hydroxyapatites (Se-Sr-HA) at equal molar ratios of x Se/(Se + P) and x Sr/(Sr + Ca) at (x = 0, 0.01, 0.03, 0.05, 0.1, and 0.2) were synthesized via the wet precipitation route and sintered at 900 °C. The effect of the two-ion concentration on morphology, surface charge, composition, antibacterial ability, and cell viability were studied. X-ray diffraction verified the phase purity and confirmed the substitution of selenium and strontium ions. Acellular in vitro bioactivity tests revealed that Se-Sr-HA was highly bioactive compared to pure HA. Se-Sr-HA samples showed excellent antibacterial activity against both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus carnosus) bacterial strains. In vitro cell-material interaction, using human osteosarcoma cells MG-63 studied by WST-8 assay, showed that Se-HA has a cytotoxic effect; however, the co-substitution of strontium in Se-HA offsets the negative impact of selenium and enhanced the biological properties of HA. Hence, the prepared samples are a suitable choice for antibacterial coatings and bone filler applications.

SAR-CoV-2 infection, emerging new variants and the role of activation induced cytidine deaminase (AID) in lasting immunity.

As the world faces a fourth COVID-19 spike, scientists are learning a lot more about the new SARS-CoV-2 strains that were previously unknown. Currently, the Delta versions of SARS-CoV-2 have become the prevalent strains in much of the world since it first appeared in India in late 2020. Researchers believe they have discovered why Delta has been so successful: those infected with it create significantly more virus than those infected with the original strain of SARS-CoV-2, making it extremely contagious. This has redirected the focus to how our immune system defends us from these various pathogens and initiates such varied responses. Hundreds of research papers have been published on the origins of long-lasting immune responses and disparities in the numbers of different immune cell types in COVID 19 survivors, but the primary architect of these discrepancies has yet to be discovered. In this essay, we will concentrate on the primary architect protein, activation induced cytidine deaminase (AID), which triggers molecular processes that allow our immune system to produce powerful antibodies and SARS-CoV-2 specific B cells, allowing us to outwit the virus. We believe that if we ever achieve permanent immunity to SARS-CoV-2 infection, AID will be the key to releasing it.

Selection and screening of drought tolerant high yielding chickpea genotypes based on physio-biochemical indices and multi-environmental yield trials.

BACKGROUND: Chickpea is one of the major legume crops being cultivated in the arid and semi-arid regions of Pakistan. It is mainly grown on the marginal areas where, terminal drought stress is one of the serious threats to its productivity. For defining the appropriate selection criteria for screening drought tolerant chickpea genotypes, present study was conducted. Distinct chickpea germplasm was collected from different pulses breeding institutes of Pakistan and evaluated for drought tolerance at germination and early seedling stages, furthermore, at late vegetative growth stages physiochemical traits and multi-environment yield performance were also tested. RESULTS: Chickpea genotypes under different environments, were significantly varied for different seedling traits, physio-chemical attributes and seed yield. Genotypes showing drought tolerance by performing better at an early seedling stages were not correspondingly high yielding. Screening for drought tolerance on seed yield basis is the most appropriate trait to develop the drought tolerant as well as high yielding chickpea genotypes. Results confirmed that traits of early growth stages were not reflecting the drought tolerance at terminal growth stages and also did not confer high yielding. NIAB-rain fed environment proved ideal in nature to screen the chickpea genotypes whereas, NIAB-lysimeter and Kalur Kot was least effective for selecting genotypes with high seed yield. Genotypes D0091-10, K010-10, D0085-10, K005-10, D0078-10, 08AG016, 08AG004, D0080-10, 09AG002, K002-10 and D0099-10 were high yielding and drought tolerant based on their performance across multiple hotspot environments. CONCLUSIONS: The selected genotypes are intended for further evaluation for varietal approval to recommend for general cultivation on farmer fields in drought hit areas of Pakistan. Among physio-biochemical traits, higher proline, glycine betain, RWC and CMS were reflecting the higher capability to tolerate the drought stress in chickpea. Drought sensitive genotypes (K0037-10, 2204, K0052-10, 09AG015, K0042-10, CM709/06, K0068-10, K004-10, K0026-10 and K0063-10) were also identified in present study which were resourceful asset for using as contrasting parents in hybridization programs. To our knowledge, this is first report using an integrated approach involving, physio-biochemical indices, and multi-environmental yield trials, for comparison, screening and selection of chickpea genotypes for drought tolerance.

Core-Shell FeSe2 /C Nanostructures Embedded in a Carbon Framework as a Free Standing Anode for a Sodium Ion Battery.

Embedding the functional nanostructures into a lightweight nanocarbon framework is very promising for developing high performance advanced electrodes for rechargeable batteries. Here, to realize workable capacity, core-shell (FeSe2 /C) nanostructures are embedded into carbon nanotube (CNT) framework via a facile wet-chemistry approach accompanied by thermally induced selenization. The CNT framework offers 3D continuous routes for electronic/ionic transfer, while macropores provide adequate space for high mass loading of FeSe2 /C. However, the carbon shell not only creates a solid electronic link among CNTs and FeSe2 but also improves the diffusivity of sodium ions into FeSe2 , as well as acts as a buffer cushion to accommodate the volume variations. These unique structural features of CNT/FeSe2 /C make it an excellent host for sodium storage with a capacity retention of 546 mAh g-1 even after 100 cycles at 100 mA g-1 . Moreover, areal and volumetric capacities of 5.06 mAh cm-2 and 158 mAh cm-3 are also achieved at high mass loading 16.9 mg cm-2 , respectively. The high performance of multi-benefited engineered structure makes it a potential candidate for secondary ion batteries, while its easy synthesis makes it extendable to further complex structures with other morphologies (such as nanorods, nanowires, etc.) to meet the high energy demands.

TiO2 nanotube array-modified electrodes for L-cysteine biosensing: experimental and density-functional theory study.

We report a non-enzymatic facile method for the detection of L-cysteine (L-Cyst) using free-standing TiO2 nanotube (TNT) array-modified glassy carbon electrodes (GCEs). Self-organized, highly ordered, and vertically oriented TNT arrays were fabricated by anodization of titanium sheets in ethylene glycol-based electrolyte. Detailed electrochemical measurements were performed and it was found that modified GCE exhibited high current compared to the pristine counterpart. The high current of the modified electrode was attributed to the high surface area and enhanced electrocatalytic activities of the TNTs toward the L-Cyst oxidation. Under the optimum conditions, the modified electrode exhibited a high sensitivity of ∼1.68 µA mM-1 cm-2 with a low detection limit of ∼0.1 mM. The fabricated electrode was found to be sensitive to pH and electrolyte temperature. The real sample analysis of the proposed method showed a decent recovery toward L-Cyst addition in human blood serum. Furthermore, the density-funcational theory (DFT) analysis revealed that TNTs have greater affinity toward L-Cyst, having stronger binding distance after its adsorption. The higher negative E ads values suggested a stable and chemisorption nature. The density of states results show that the E gap of TNTs is significantly reduced after L-Cyst adsorption. The modified GCE showed excellent selectivity, enhanced stability, and fast response, which make TNTs a promising candidate for the enzyme-free detection of other biological analytes.

Regulation of the positive transcriptional effect of PLZF through a non-canonical EZH2 activity.

The transcription factor PLZF (promyelocytic leukemia zinc finger protein) acts as an epigenetic regulator balancing self-renewal and differentiation of hematopoietic cells through binding to various chromatin-modifying factors. First described as a transcriptional repressor, PLZF is also associated with active transcription, although the molecular bases underlying the differences are unknown. Here, we reveal that in a hematopoietic cell line, PLZF is predominantly associated with transcribed genes. Additionally, we identify a new association between PLZF and the histone methyltransferase, EZH2 at the genomic level. We find that co-occupancy of PLZF and EZH2 on chromatin at PLZF target genes is not associated with SUZ12 or trimethylated lysine 27 of histone H3 (H3K27me3) but with the active histone mark H3K4me3 and active transcription. Removal of EZH2 leads to an increase of PLZF binding and increased gene expression. Our results suggest a new role of EZH2 in restricting PLZF positive transcriptional activity independently of its canonical PRC2 activity.

ARS2 is a general suppressor of pervasive transcription.

Termination of transcription is important for establishing gene punctuation marks. It is also critical for suppressing many of the pervasive transcription events occurring throughout eukaryotic genomes and coupling their RNA products to efficient decay. In human cells, the ARS2 protein has been implicated in such function as its depletion causes transcriptional read-through of selected gene terminators and because it physically interacts with the ribonucleolytic nuclear RNA exosome. Here, we study the role of ARS2 on transcription and RNA metabolism genome wide. We show that ARS2 depletion negatively impacts levels of promoter-proximal RNA polymerase II at protein-coding (pc) genes. Moreover, our results reveal a general role of ARS2 in transcription termination-coupled RNA turnover at short transcription units like snRNA-, replication-dependent histone-, promoter upstream transcript- and enhancer RNA-loci. Depletion of the ARS2 interaction partner ZC3H18 mimics the ARS2 depletion, although to a milder extent, whereas depletion of the exosome core subunit RRP40 only impacts RNA abundance post-transcriptionally. Interestingly, ARS2 is also involved in transcription termination events within first introns of pc genes. Our work therefore establishes ARS2 as a general suppressor of pervasive transcription with the potential to regulate pc gene expression.