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Frontiers in Plant Science 2022Tandem CCCH zinc finger (TZF) proteins are the essential components of processing bodies (PBs) and stress granules (SGs), which play critical roles in growth development...
Tandem CCCH zinc finger (TZF) proteins are the essential components of processing bodies (PBs) and stress granules (SGs), which play critical roles in growth development and stress response in both animals and plants through posttranscriptional regulation of target mRNA. In this study, we characterized the biological and molecular functions of a novel tandem zinc finger protein, OsTZF7. The expression of was upregulated by abiotic stresses, including polyethylene glycol (PEG) 4000, NaCl, and abscisic acid (ABA) in rice. Accordingly, the overexpression of increased drought tolerance and enhanced sensitivity to exogenous ABA in rice, whereas the knockdown of resulted in the opposite phenotype. RNA-seq analysis revealed that genes related to "response to stress," "abscisic acid signaling," "methylated histone binding," and "cytoplasmic mRNA processing body" are regulated by . We demonstrated that OsTZF7 can traffic between the nucleus and PBs/SGs, and the leucine-rich nuclear export signal (NES) mediates the nuclear export of OsTZF7. Additionally, we revealed that OsTZF7 can bind adenine- and uridine-rich (AU-rich) element (ARE) or ARE-like motifs within the 3' untranslated region of downregulated mRNAs, and interact with PWWP family proteins . Together, these results indicate that OsTZF7 positively regulates drought response in rice ABA signaling and may be involved in mRNA turnover.
PubMed: 35265093
DOI: 10.3389/fpls.2022.802337 -
Viruses Mar 2016Enteroviruses such as poliovirus (PV) and coxsackievirus B3 (CVB3) have evolved several parallel strategies to regulate cellular gene expression and stress responses to... (Review)
Review
Enteroviruses such as poliovirus (PV) and coxsackievirus B3 (CVB3) have evolved several parallel strategies to regulate cellular gene expression and stress responses to ensure efficient expression of the viral genome. Enteroviruses utilize their encoded proteinases to take over the cellular translation apparatus and direct ribosomes to viral mRNAs. In addition, viral proteinases are used to control and repress the two main types of cytoplasmic RNA granules, stress granules (SGs) and processing bodies (P-bodies, PBs), which are stress-responsive dynamic structures involved in repression of gene expression. This review discusses these processes and the current understanding of the underlying mechanisms with respect to enterovirus infections. In addition, the review discusses accumulating data suggesting linkage exists between RNA granule formation and innate immune sensing and activation.
Topics: Animals; Cytoplasmic Granules; Enterovirus; Enterovirus Infections; Gene Expression Regulation; Host-Pathogen Interactions; Humans; Immunity, Innate; Protein Biosynthesis; Proteolysis; RNA Caps; RNA, Viral; Signal Transduction; Stress, Physiological
PubMed: 27043612
DOI: 10.3390/v8040093 -
Nature Communications Jul 2023Prediction, prevention and treatment of virus infections require understanding of cell-to-cell variability that leads to heterogenous disease outcomes, but the source of...
Prediction, prevention and treatment of virus infections require understanding of cell-to-cell variability that leads to heterogenous disease outcomes, but the source of this heterogeneity has yet to be clarified. To study the multimodal response of single human cells to herpes simplex virus type 1 (HSV-1) infection, we mapped high-dimensional viral and cellular state spaces throughout the infection using multiplexed imaging and quantitative single-cell measurements of viral and cellular mRNAs and proteins. Here we show that the high-dimensional cellular state scape can predict heterogenous infections, and cells move through the cellular state landscape according to infection progression. Spatial information reveals that infection changes the cellular state of both infected cells and of their neighbors. The multiplexed imaging of HSV-1-induced cellular modifications links infection progression to changes in signaling responses, transcriptional activity, and processing bodies. Our data show that multiplexed quantification of responses at the single-cell level, across thousands of cells helps predict infections and identify new targets for antivirals.
Topics: Humans; Herpesvirus 1, Human; Herpes Simplex; Antiviral Agents; RNA, Messenger; Virus Replication
PubMed: 37500668
DOI: 10.1038/s41467-023-40148-6 -
Wiley Interdisciplinary Reviews. RNA 2013RNA granules are structures within cells that play major roles in gene expression and homeostasis. Two principle kinds of RNA granules are conserved from yeast to... (Review)
Review
RNA granules are structures within cells that play major roles in gene expression and homeostasis. Two principle kinds of RNA granules are conserved from yeast to mammals: stress granules (SGs), which contain stalled translation initiation complexes, and processing bodies (P-bodies, PBs), which are enriched with factors involved in RNA turnover. Since RNA granules are associated with silenced transcripts, viruses subvert RNA granule function for replicative advantages. This review, focusing on RNA viruses, discusses mechanisms that manipulate stress granules and P-bodies to promote synthesis of viral proteins. Three main themes have emerged for how viruses manipulate RNA granules; (1) cleavage of key host factors, (2) control of protein kinase R (PKR) activation, and (3) redirecting RNA granule components for new or parallel roles in viral reproduction, at the same time disrupting RNA granules. Viruses utilize one or more of these routes to achieve robust and productive infection.
Topics: Cytoplasmic Granules; Host-Pathogen Interactions; Macromolecular Substances; RNA Viruses; Viral Proteins; Virus Replication
PubMed: 23554219
DOI: 10.1002/wrna.1162 -
RNA Biology Jun 2017Spliceosomal snRNPs are complex particles that proceed through a fascinating maturation pathway. Several steps of this pathway are closely linked to nuclear non-membrane... (Review)
Review
Spliceosomal snRNPs are complex particles that proceed through a fascinating maturation pathway. Several steps of this pathway are closely linked to nuclear non-membrane structures called Cajal bodies. In this review, I summarize the last 20 y of research in this field. I primarily focus on snRNP biogenesis, specifically on the steps that involve Cajal bodies. I also evaluate the contribution of the Cajal body in snRNP quality control and discuss the role of snRNPs in Cajal body formation.
Topics: Animals; Coiled Bodies; Humans; Protein Binding; RNA Processing, Post-Transcriptional; Ribonucleoproteins, Small Nuclear; Spliceosomes; Transcription, Genetic
PubMed: 27627834
DOI: 10.1080/15476286.2016.1231359 -
Journal of Molecular Biology Jan 2022Condensation, or liquid-like phase separation, is a phenomenon indispensable for the spatiotemporal regulation of molecules within the cell. Recent studies indicate that...
Condensation, or liquid-like phase separation, is a phenomenon indispensable for the spatiotemporal regulation of molecules within the cell. Recent studies indicate that the composition and molecular organization of phase-separated organelles such as Stress Granules (SGs) and Processing Bodies (PBs) are highly variable and dynamic. A dense contact network involving both RNAs and proteins controls the formation of SGs and PBs and an intricate molecular architecture, at present poorly understood, guarantees that these assemblies sense and adapt to different stresses and environmental changes. Here, we investigated the physico-chemical properties of SGs and PBs components and studied the architecture of their interaction networks. We found that proteins and RNAs establishing the largest amount of contacts in SGs and PBs have distinct properties and intrinsic disorder is enriched in all protein-RNA, protein-protein and RNA-RNA interaction networks. The increase of disorder in proteins is accompanied by an enrichment in single-stranded regions of RNA binding partners. Our results suggest that SGs and PBs quickly assemble and disassemble through dynamic contacts modulated by unfolded domains of their components.
Topics: Cell Line; Humans; Processing Bodies; RNA; RNA-Binding Proteins; Stress Granules
PubMed: 34274326
DOI: 10.1016/j.jmb.2021.167159 -
Virology Feb 2013RNA granules are structures within cells that impart key regulatory measures on gene expression. Two general types of RNA granules are conserved from yeast to mammals:... (Review)
Review
RNA granules are structures within cells that impart key regulatory measures on gene expression. Two general types of RNA granules are conserved from yeast to mammals: stress granules (SGs), which contain many translation initiation factors, and processing bodies (P-bodies, PBs), which are enriched for proteins involved in RNA turnover. Because of the inverse relationship between appearance of RNA granules and persistence of translation, many viruses must subvert RNA granule function for replicative purposes. Here we discuss the viruses and mechanisms that manipulate stress granules and P-bodies to promote synthesis of viral proteins. Several themes have emerged for manipulation of RNA granules by viruses: (1) disruption of RNA granules at the mid-phase of infection, (2) prevention of RNA granule assembly throughout infection and (3) co-opting of RNA granule proteins for new or parallel roles in viral reproduction. Viruses must employ one or multiple of these routes for a robust and productive infection to occur. The possible role for RNA granules in promoting innate immune responses poses an additional reason why viruses must counteract the effects of RNA granules for efficient replication.
Topics: Animals; Cytoplasmic Granules; Humans; Macromolecular Substances; Models, Biological; Multienzyme Complexes; RNA, Viral; Viral Proteins; Virus Physiological Phenomena; Virus Replication; Yeasts
PubMed: 23290869
DOI: 10.1016/j.virol.2012.11.017 -
Nature Communications Oct 2019Liquid-liquid phase separation is increasingly recognized as a process involved in cellular organization. Thus far, a detailed structural characterization of this...
Liquid-liquid phase separation is increasingly recognized as a process involved in cellular organization. Thus far, a detailed structural characterization of this intrinsically heterogeneous process has been challenging. Here we combine solid- and solution-state NMR spectroscopy to obtain atomic-level insights into the assembly and maturation of cytoplasmic processing bodies that contain mRNA as well as enzymes involved in mRNA degradation. In detail, we have studied the enhancer of decapping 3 (Edc3) protein that is a central hub for processing body formation in yeast. Our results reveal that Edc3 domains exhibit diverse levels of structural organization and dynamics after liquid-liquid phase separation. In addition, we find that interactions between the different Edc3 domains and between Edc3 and RNA in solution are largely preserved in the condensed protein state, allowing processing bodies to rapidly form and dissociate upon small alterations in the cellular environment.
Topics: Hydrophobic and Hydrophilic Interactions; Nuclear Magnetic Resonance, Biomolecular; Protein Domains; RNA Stability; RNA, Fungal; RNA, Messenger; Schizosaccharomyces pombe Proteins; Static Electricity
PubMed: 31586050
DOI: 10.1038/s41467-019-12402-3 -
Frontiers in Cellular and Infection... 2019Regulation of RNA homeostasis or "RNAstasis" is a central step in eukaryotic gene expression. From transcription to decay, cellular messenger RNAs (mRNAs) associate with... (Review)
Review
Regulation of RNA homeostasis or "RNAstasis" is a central step in eukaryotic gene expression. From transcription to decay, cellular messenger RNAs (mRNAs) associate with specific proteins in order to regulate their entire cycle, including mRNA localization, translation and degradation, among others. The best characterized of such RNA-protein complexes, today named membraneless organelles, are Stress Granules (SGs) and Processing Bodies (PBs) which are involved in RNA storage and RNA decay/storage, respectively. Given that SGs and PBs are generally associated with repression of gene expression, viruses have evolved different mechanisms to counteract their assembly or to use them in their favor to successfully replicate within the host environment. In this review we summarize the current knowledge about the viral regulation of SGs and PBs, which could be a potential novel target for the development of broad-spectrum antiviral therapies.
Topics: Animals; Cytoplasmic Granules; Gene Expression Regulation; Gene Expression Regulation, Viral; Host-Pathogen Interactions; Humans; Organelles; Signal Transduction; Stress, Physiological; Virus Diseases; Virus Physiological Phenomena; Virus Replication; Viruses
PubMed: 31681621
DOI: 10.3389/fcimb.2019.00336 -
Viruses Jun 2016The general stress and innate immune responses are closely linked and overlap at many levels. The outcomes of these responses serve to reprogram host expression patterns... (Review)
Review
The general stress and innate immune responses are closely linked and overlap at many levels. The outcomes of these responses serve to reprogram host expression patterns to prevent viral invasions. In turn, viruses counter attack these cell responses to ensure their replication. The mechanisms by which viruses attempt to control host cell responses are as varied as the number of different virus families. One of the most recurrent strategies used by viruses to control the antiviral response of the cell is to hijack the translation machinery of the host, such that viral proteins are preferentially synthesized, while the expression of the stress and antiviral responses of the cell are blocked at the translation level. Here, we will review how rotaviruses, an important agent of acute severe gastroenteritis in children, overcome the stress responses of the cell to establish a productive infectious cycle.
Topics: Gene Expression Regulation; Host-Pathogen Interactions; Humans; Immunity, Innate; Protein Biosynthesis; Rotavirus; Rotavirus Infections; Stress, Physiological; Virus Replication
PubMed: 27338442
DOI: 10.3390/v8060162