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International Journal of Molecular... Jun 2021Nucleolar stress occurs when ribosome production or function declines. Nucleolar stress in stem cells or progenitor cells often leads to disease states called...
Nucleolar stress occurs when ribosome production or function declines. Nucleolar stress in stem cells or progenitor cells often leads to disease states called ribosomopathies. offers a robust system to explore how nucleolar stress causes cell cycle arrest, apoptosis, or autophagy depending on the cell type. We provide an overview of nucleolar stress in by depleting nucleolar phosphoprotein of 140 kDa (Nopp140), a ribosome biogenesis factor (RBF) in nucleoli and Cajal bodies (CBs). The depletion of Nopp140 in eye imaginal disc cells generates eye deformities reminiscent of craniofacial deformities associated with the Treacher Collins syndrome (TCS), a human ribosomopathy. We show the activation of c-Jun N-terminal Kinase (JNK) in larvae homozygous for a gene deletion. JNK is known to induce the expression of the pro-apoptotic Hid protein and autophagy factors Atg1, Atg18.1, and Atg8a; thus, JNK is a central regulator in nucleolar stress. Ribosome abundance declines upon Nopp140 loss, but unusual cytoplasmic granules accumulate that resemble Processing (P) bodies based on marker proteins, Decapping Protein 1 (DCP1) and Maternal expression at 31B (Me31B). Wild type brain neuroblasts (NBs) express copious amounts of endogenous coilin, but coilin levels decline upon nucleolar stress in most NB types relative to the Mushroom body (MB) NBs. MB NBs exhibit resilience against nucleolar stress as they maintain normal coilin, Deadpan, and EdU labeling levels.
Topics: Animals; CRISPR-Cas Systems; Cell Nucleolus; Coiled Bodies; Drosophila Proteins; Drosophila melanogaster; Gene Expression Regulation, Developmental; Larva; Phosphoproteins; RNA-Binding Proteins; Ribosomes; Stress, Physiological
PubMed: 34201772
DOI: 10.3390/ijms22136759 -
Heliyon Sep 2023This review highlights the critical concern foreign material contamination poses across the food processing industry and provides information on methods and... (Review)
Review
This review highlights the critical concern foreign material contamination poses across the food processing industry and provides information on methods and implementations to minimize the hazards caused by foreign materials. A foreign material is defined as any non-food, foreign bodies that may cause illness or injury to the consumer and are not typically part of the food. Foreign materials can enter the food processing plant as part of the raw materials such as fruit pits, bones, or contaminants like stones, insects, soil, grit, or pieces of harvesting equipment. Over the past 20 years, foreign materials have been responsible for about one out of ten recalls of foods, with plastic fragments being the most common complaint. The goal of this paper is to further the understanding of the risks foreign materials are to consumers and the tools that could be used to minimize the risk of foreign objects in foods.
PubMed: 37809834
DOI: 10.1016/j.heliyon.2023.e19574 -
Proceedings of the National Academy of... Apr 2023Many biomolecular condensates appear to form through liquid-liquid phase separation (LLPS). Individual condensate components can often undergo LLPS in vitro, capturing...
Many biomolecular condensates appear to form through liquid-liquid phase separation (LLPS). Individual condensate components can often undergo LLPS in vitro, capturing some features of the native structures. However, natural condensates contain dozens of components with different concentrations, dynamics, and contributions to compartment formation. Most biochemical reconstitutions of condensates have not benefited from quantitative knowledge of these cellular features nor attempted to capture natural complexity. Here, we build on prior quantitative cellular studies to reconstitute yeast RNA processing bodies (P bodies) from purified components. Individually, five of the seven highly concentrated P-body proteins form homotypic condensates at cellular protein and salt concentrations, using both structured domains and intrinsically disordered regions. Combining the seven proteins together at their cellular concentrations with RNA yields phase-separated droplets with partition coefficients and dynamics of most proteins in reasonable agreement with cellular values. RNA delays the maturation of proteins within and promotes the reversibility of, P bodies. Our ability to quantitatively recapitulate the composition and dynamics of a condensate from its most concentrated components suggests that simple interactions between these components carry much of the information that defines the physical properties of the cellular structure.
Topics: Processing Bodies; Saccharomyces cerevisiae; RNA
PubMed: 36972455
DOI: 10.1073/pnas.2214064120 -
Nature Communications Aug 2023Ethylene plays essential roles in rice growth, development and stress adaptation. Translational control of ethylene signaling remains unclear in rice. Here, through...
Ethylene plays essential roles in rice growth, development and stress adaptation. Translational control of ethylene signaling remains unclear in rice. Here, through analysis of an ethylene-response mutant mhz9, we identified a glycine-tyrosine-phenylalanine (GYF) domain protein MHZ9, which positively regulates ethylene signaling at translational level in rice. MHZ9 is localized in RNA processing bodies. The C-terminal domain of MHZ9 interacts with OsEIN2, a central regulator of rice ethylene signaling, and the N-terminal domain directly binds to the OsEBF1/2 mRNAs for translational inhibition, allowing accumulation of transcription factor OsEIL1 to activate the downstream signaling. RNA-IP seq and CLIP-seq analyses reveal that MHZ9 associates with hundreds of RNAs. Ribo-seq analysis indicates that MHZ9 is required for the regulation of ~ 90% of genes translationally affected by ethylene. Our study identifies a translational regulator MHZ9, which mediates translational regulation of genes in response to ethylene, facilitating stress adaptation and trait improvement in rice.
Topics: Oryza; Plant Proteins; Mutation; Ethylenes; RNA; Gene Expression Regulation, Plant
PubMed: 37542048
DOI: 10.1038/s41467-023-40429-0 -
Genes Aug 2023has been a premier model organism for over a century and many discoveries in flies have furthered our understanding of human disease. Flies have been successfully... (Review)
Review
has been a premier model organism for over a century and many discoveries in flies have furthered our understanding of human disease. Flies have been successfully applied to many aspects of health-based research spanning from behavioural addiction, to dysplasia, to RNA dysregulation and protein misfolding. Recently, tissues have been used to study biomolecular condensates and their role in multicellular systems. Identified in a wide range of plant and animal species, biomolecular condensates are dynamic, non-membrane-bound sub-compartments that have been observed and characterised in the cytoplasm and nuclei of many cell types. Condensate biology has exciting research prospects because of their diverse roles within cells, links to disease, and potential for therapeutics. In this review, we will discuss processing bodies (P bodies), a conserved biomolecular condensate, with a particular interest in how can be applied to advance our understanding of condensate biogenesis and their role in disease.
Topics: Animals; Humans; Drosophila; Processing Bodies; Cell Nucleus; Cytoplasm; RNA
PubMed: 37761815
DOI: 10.3390/genes14091675 -
Proceedings of the National Academy of... Sep 2023MicroRNAs (miRNAs) play an important role in gene regulation. In , mature miRNAs are processed from primary miRNA transcripts by the Dicing complex that contains...
MicroRNAs (miRNAs) play an important role in gene regulation. In , mature miRNAs are processed from primary miRNA transcripts by the Dicing complex that contains Dicer-like 1 (DCL1), SERRATE (SE), and Hyponastic Leaves 1 (HYL1). The Dicing complex can form nuclear dicing bodies (D-bodies) through SE phase separation. Here, we report that Cyclophilin71 (CYP71), a peptidyl-prolyl isomerase (PPIase), positively regulates miRNA processing. We show that CYP71 directly interacts with SE and enhances its phase separation, thereby promoting the formation of D-body and increasing the activity of the Dicing complex. We further show that the PPIase activity is important for the function of CYP71 in miRNA production. Our findings reveal orchestration of miRNA processing by a cyclophilin protein and suggest the involvement of peptidyl-prolyl isomerization, a structural mechanism, in SE phase separation and miRNA processing.
Topics: Arabidopsis; Cyclophilins; MicroRNAs; Plant Leaves; RNA-Binding Proteins; Arabidopsis Proteins
PubMed: 37639607
DOI: 10.1073/pnas.2305244120 -
Neuron Sep 2022Prethalamic nuclei in the mammalian brain include the zona incerta, the ventral lateral geniculate nucleus, and the intergeniculate leaflet, which provide long-range... (Review)
Review
Prethalamic nuclei in the mammalian brain include the zona incerta, the ventral lateral geniculate nucleus, and the intergeniculate leaflet, which provide long-range inhibition to many targets in the midbrain, hindbrain, and thalamus. These nuclei in the caudal prethalamus can integrate sensory and non-sensory information, and together they exert powerful inhibitory control over a wide range of brain functions and behaviors that encompass most aspects of the behavioral repertoire of mammals, including sleep, circadian rhythms, feeding, drinking, predator avoidance, and exploration. In this perspective, we highlight the evidence for this wide-ranging control and lay out the hypothesis that one role of caudal prethalamic nuclei may be that of a behavioral switchboard that-depending on the sensory input, the behavioral context, and the state of the animal-can promote a behavioral strategy and suppress alternative, competing behaviors by modulating inhibitory drive onto diverse target areas.
Topics: Animals; Behavior Control; Circadian Rhythm; Geniculate Bodies; Mammals; Mesencephalon; Thalamus
PubMed: 36076337
DOI: 10.1016/j.neuron.2022.07.018 -
Nature Communications Jun 2022The formation of membraneless organelles can be a proteotoxic stress control mechanism that locally condenses a set of components capable of mediating protein...
The formation of membraneless organelles can be a proteotoxic stress control mechanism that locally condenses a set of components capable of mediating protein degradation decisions. The breadth of mechanisms by which cells respond to stressors and form specific functional types of membraneless organelles, is incompletely understood. We found that Bcl2-associated athanogene 2 (BAG2) marks a distinct phase-separated membraneless organelle, triggered by several forms of stress, particularly hyper-osmotic stress. Distinct from well-known condensates such as stress granules and processing bodies, BAG2-containing granules lack RNA, lack ubiquitin and promote client degradation in a ubiquitin-independent manner via the 20S proteasome. These organelles protect the viability of cells from stress and can traffic to the client protein, in the case of Tau protein, on the microtubule. Components of these ubiquitin-independent degradation organelles include the chaperone HSP-70 and the 20S proteasome activated by members of the PA28 (PMSE) family. BAG2 condensates did not co-localize with LAMP-1 or p62/SQSTM1. When the proteasome is inhibited, BAG2 condensates and the autophagy markers traffic to an aggresome-like structure.
Topics: Autophagy; Humans; Molecular Chaperones; Proteasome Endopeptidase Complex; Proteolysis; Ubiquitin
PubMed: 35654899
DOI: 10.1038/s41467-022-30751-4 -
Current Genetics Feb 2020The eukaryotic cell is subdivided into distinct functional domains by the presence of both membrane-bound and membraneless organelles. The latter include cytoplasmic... (Review)
Review
The eukaryotic cell is subdivided into distinct functional domains by the presence of both membrane-bound and membraneless organelles. The latter include cytoplasmic granules, like the Processing-body (P-body), that are induced in response to stress and contain specific sets of mRNAs and proteins. Although P-bodies have been evolutionarily conserved, we do not yet understand the full extent of their biological functions in the cell. Early studies suggested that these structures might be sites of mRNA decay as the first protein constituents identified were enzymes involved in mRNA processing. However, more recent work indicates that this is not likely to be the primary function of these granules and has even suggested that P-bodies are sites of long-term mRNA storage. Interestingly, P-bodies and other ribonucleoprotein granules have been found to also contain a variety of signaling molecules, including protein kinases and phosphatases key to the normal control of cell growth and survival. Therefore, P-bodies could have a role in the modulation of cell signaling during particular types of stress. This review discusses both the general implications of such a proposal and one particular example that illustrates how the granule recruitment of a protein kinase can impact overall cell physiology.
Topics: Cytoplasmic Granules; Eukaryotic Cells; Gene Expression Regulation; Organelles; RNA Processing, Post-Transcriptional; RNA Stability; RNA, Messenger; Signal Transduction; Vault Ribonucleoprotein Particles
PubMed: 31317215
DOI: 10.1007/s00294-019-01016-3 -
Plants (Basel, Switzerland) Feb 2022Based on prior knowledge and with the support of new methodology, solid progress in the understanding of seed life has taken place over the few last years. This update... (Review)
Review
Based on prior knowledge and with the support of new methodology, solid progress in the understanding of seed life has taken place over the few last years. This update reflects recent advances in three key traits of seed life (i.e., preharvest sprouting, genomic imprinting, and stored-mRNA). The first breakthrough refers to cloning of the mitogen-activated protein kinase-kinase 3 (MKK3) gene in barley and wheat. MKK3, in cooperation with ABA signaling, controls seed dormancy. This advance has been determinant in producing improved varieties that are resistant to preharvest sprouting. The second advance concerns to uniparental gene expression (i.e., imprinting). Genomic imprinting primarily occurs in the endosperm. Although great advances have taken place in the last decade, there is still a long way to go to complete the puzzle regarding the role of genomic imprinting in seed development. This trait is probably one of the most important epigenetic facets of developing endosperm. An example of imprinting regulation is polycomb repressive complex 2 (PRC2). The mechanism of PRC2 recruitment to target endosperm with specific genes is, at present, robustly studied. Further progress in the knowledge of recruitment of PRC2 epigenetic machinery is considered in this review. The third breakthrough referred to in this update involves stored mRNA. The role of the population of this mRNA in germination is far from known. Its relations to seed aging, processing bodies (P bodies), and RNA binding proteins (RBPs), and how the stored mRNA is targeted to monosomes, are aspects considered here. Perhaps this third trait is the one that will require greater experimental dedication in the future. In order to make progress, herein are included some questions that are needed to be answered.
PubMed: 35214823
DOI: 10.3390/plants11040490