Climate change and plastic pollution are two main issues that our world is currently facing, and they are mainly linked through various processes, mechanisms, and chemical blueprint. Emerging issues related to microplastic (MP) contamination in freshwater are expanding and diverse research is being carried out globally. Factors causing climate change are increasing the frequency of extreme weather phenomena such as floods, drought, sea level rise, and heat waves, which can directly or indirectly influence the plastic/MP contamination in various ecosystems including groundwater environments.
View Article and Find Full Text PDFThe chirality of a chemical differentiates it from its mirror-image counterpart. This unique property has significant implications in chemistry, biology, and drug discovery, where chiral chemicals display high selectivity and activity in achieving target specificity and reducing attrition rates in drug development. Stress granules (SGs) are dynamic assemblies of proteins and RNA that form in the cytoplasm of cells under stress conditions.
View Article and Find Full Text PDFGroundwater Charge was introduced in 2005 as one of the sustainable resource management measures in South Korea. The implementation rate, however, stagnated around 37 %, indicating that most local governments chose not to adopt this 'optional' regulation. While previous Stakeholder Analysis studies mainly blamed exclusion - or limited involvement - of stakeholders in the designing and structuring stage of policy-making process for policy failures, this study focused on the interest conflicts and dynamics hindered implementation process.
View Article and Find Full Text PDFBiochem Biophys Res Commun
February 2024
Stress granule (SG) is a temporary cellular structure that plays a crucial role in the regulation of mRNA and protein sequestration during various cellular stress conditions. SG enables cells to cope with stress more effectively, conserving vital energy and resources. Focusing on the NTF2-like domain of G3BP1, a key protein in SG dynamics, we explore to identify and characterize novel small molecules involved in SG modulation without external stressors.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
September 2023
Mammalian encodes a protein precursor of Irisin, which is important for exercise-dependent regulation of whole-body metabolism. In a genetic screen in , we identified (), which shows substantial protein homology to mouse and human , as a regulator of autophagy acting downstream of Atg1/Atg13. Physiologically, -deficient flies showed reduced exercise performance and defective cold resistance, which were rescued by exogenous expression of .
View Article and Find Full Text PDFNat Struct Mol Biol
October 2023
Stress granules are biomolecular condensates composed of protein and mRNA. One feature of stress granule-enriched mRNAs is that they are often longer than average. Another feature of stress granule-enriched mRNAs is that they often contain multiple N-methyladenosine (mA) residues.
View Article and Find Full Text PDFTransposable elements (TEs) are DNA sequences that can transpose and replicate within the genome, leading to genetic changes that affect various aspects of host biology. Evolutionarily, hosts have also developed molecular mechanisms to suppress TEs at the transcriptional and post-transcriptional levels. Recent studies suggest that stress-induced formation of ribonucleoprotein (RNP) granules, including stress granule (SG) and processing body (P-body), can play a role in the sequestration of TEs to prevent transposition, suggesting an additional layer of the regulatory mechanism for TEs.
View Article and Find Full Text PDFStress granules (SGs) are stress-induced subcellular compartments, which carry out a particular function to cope with stress. These granules protect cells from stress-related damage and cell death through dynamic sequestration of numerous ribonucleoproteins (RNPs) and signaling proteins, thereby promoting cell survival under both physiological and pathological condition. During tumorigenesis, cancer cells are repeatedly exposed to diverse stress stimuli from the tumor microenvironment, and the dynamics of SGs is often modulated due to the alteration of gene expression patterns in cancer cells, leading to tumor progression as well as resistance to anticancer treatment.
View Article and Find Full Text PDFThe ligand of numb-protein X1 () acts as a proto-oncogene by inhibiting stability; however, the regulation of expression has not been investigated. In this study, we screened chemicals to identify factors that potentially regulate expression. We found that expression levels were decreased by DNA damage, including that by cisplatin.
View Article and Find Full Text PDFMounting evidence supports the relationship between obesity and cancer. However, the molecular mechanisms linking obesity with cancer remain largely uninvestigated. In this study, we demonstrate that the expression of C1q/TNF-related protein 1 (CTRP1), an adiponectin paralogue, contributes to tumor growth by regulating the tumor suppressor p53.
View Article and Find Full Text PDFEvid Based Complement Alternat Med
September 2020
COVID-19, a global pandemic, has caused over 750,000 deaths worldwide as of August 2020. A vaccine or remedy for SARS-CoV-2, the virus responsible for COVID-19, is necessary to slow down the spread and lethality of COVID-19. However, there is currently no effective treatment available against SARS-CoV-2.
View Article and Find Full Text PDFDNA damage often induces heterogeneous cell-fate responses, such as cell-cycle arrest and apoptosis. Through single-cell RNA sequencing (scRNA-seq), we characterize the transcriptome response of cultured colon cancer cell lines to 5-fluorouracil (5FU)-induced DNA damage. After 5FU treatment, a single population of colon cancer cells adopts three distinct transcriptome phenotypes, which correspond to diversified cell-fate responses: apoptosis, cell-cycle checkpoint, and stress resistance.
View Article and Find Full Text PDF(Linn.) is a medicinal herbal plant that is commonly used to treat chronic kidney disease and hepatitis. However, its effect on cell proliferation has not been clearly revealed.
View Article and Find Full Text PDFExercise is among the most effective interventions for age-associated mobility decline and metabolic dysregulation. Although long-term endurance exercise promotes insulin sensitivity and expands respiratory capacity, genetic components and pathways mediating the metabolic benefits of exercise have remained elusive. Here, we show that Sestrins, a family of evolutionarily conserved exercise-inducible proteins, are critical mediators of exercise benefits.
View Article and Find Full Text PDFSestrins represent a family of stress-inducible proteins that prevent the progression of many age- and obesity-associated disorders. Endogenous Sestrins maintain insulin-dependent AKT Ser/Thr kinase (AKT) activation during high-fat diet-induced obesity, and overexpressed Sestrins activate AKT in various cell types, including liver and skeletal muscle cells. Although Sestrin-mediated AKT activation improves metabolic parameters, the mechanistic details underlying such improvement remain elusive.
View Article and Find Full Text PDFmTORC1 is a protein kinase important for metabolism and is regulated by growth factor and nutrient signaling pathways, mediated by the Rheb and Rag GTPases, respectively. Here we provide the first animal model in which both pathways were upregulated through concurrent mutations in their GTPase-activating proteins, and . Unlike former models that induced limited mTORC1 upregulation, hepatic deletion of both and (DKO) produced strong, synergistic activation of the mTORC1 pathway and provoked pronounced and widespread hepatocyte damage, leading to externally visible liver failure phenotypes, such as jaundice and systemic growth defects.
View Article and Find Full Text PDFThe well-known tumor suppressor p53 inhibits the formation of various cancers by inducing cell cycle arrest and apoptosis. Although p53 mutations are commonly found in many cancers, p53 is functionally inactivated in tumor cells that retain wild-type p53. Here, we show that the ligand of numb protein X1 (LNX1) inhibited p53-dependent transcription by decreasing the half-life of p53.
View Article and Find Full Text PDFN-methyladenosine (mA) is the most prevalent modified nucleotide in mRNA, with around 25% of mRNAs containing at least one mA. Methylation of mRNA to form mA is required for diverse cellular and physiological processes. Although the presence of mA in an mRNA can affect its fate in different ways, it is unclear how mA directs this process and why the effects of mA can vary in different cellular contexts.
View Article and Find Full Text PDFMacroautophagy (hereafter autophagy) is a well-conserved cellular process through which cytoplasmic components are delivered to the vacuole/lysosome for degradation and recycling. Studies have revealed the molecular mechanism of transcriptional regulation of autophagy-related (ATG) genes upon nutrient deprivation. However, little is known about their translational regulation.
View Article and Find Full Text PDFPost-transcriptional RNA processing is a core mechanism of gene expression control in cell stress response. The poly(A) tail influences mRNA translation and stability, but it is unclear whether there are global roles of poly(A)-tail lengths in cell stress. To address this, we developed tail-end displacement sequencing (TED-seq) for an efficient transcriptome-wide profiling of poly(A) lengths and applied it to endoplasmic reticulum (ER) stress in human cells.
View Article and Find Full Text PDFAMP-activated protein kinase (AMPK) regulates autophagy initiation when intracellular ATP level decreases. However, the role of AMPK during autophagosome maturation is not fully understood. Here, we report that AMPK contributes to efficient autophagosome maturation and lysosomal fusion.
View Article and Find Full Text PDFUpon stress, cytoplasmic mRNA is sequestered to insoluble ribonucleoprotein (RNP) granules, such as the stress granule (SG). Partially due to the belief that translationally suppressed mRNAs are recruited to SGs in bulk, stress-induced dynamic redistribution of mRNA has not been thoroughly characterized. Here, we report that endoplasmic reticulum (ER) stress targets only a small subset of translationally suppressed mRNAs into the insoluble RNP granule fraction (RG).
View Article and Find Full Text PDFAutophagy is one of the major degradative mechanisms that can eliminate excessive nutrients, toxic protein aggregates, damaged organelles and invading microorganisms. In response to obesity and obesity-associated lipotoxic, proteotoxic and oxidative stresses, autophagy plays an essential role in maintaining physiological homeostasis. However, obesity and its associated stress insults can often interfere with the autophagic process through various mechanisms, which result in further aggravation of obesity-related metabolic pathologies in multiple metabolic organs.
View Article and Find Full Text PDFConessine, a steroidal alkaloid isolated from Holarrhena floribunda, has anti-malarial activity and interacts with the histamine H3 receptor. However, the cellular effects of conessine are poorly understood. Accordingly, we evaluated the involvement of conessine in the regulation of autophagy.
View Article and Find Full Text PDFExcessive accumulation of reactive oxygen species (ROS) and chronic activation of mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) are well-characterized promoters of aging and age-associated degenerative pathologies. Sestrins, a family of highly conserved stress-inducible proteins, are important negative regulators of both ROS and mTORC1 signaling pathways; however, the mechanistic basis of how Sestrins suppress these pathways remains elusive. In the past couple of years, breakthrough discoveries about Sestrin signaling and its molecular nature have markedly increased our biochemical understanding of Sestrin function.
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