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RNA Biology 2008Processing bodies (P-bodies) have recently come to the fore as important cellular sites of mRNA degradation and translational silencing. Despite these central functions... (Review)
Review
Processing bodies (P-bodies) have recently come to the fore as important cellular sites of mRNA degradation and translational silencing. Despite these central functions in the control of gene expression, the roles of P-bodies have only been characterized in a limited number of cell types and physiological contexts. Neurons are highly plastic cells that undergo dynamic changes as new connections are made or existing ones modified. This neuronal plasticity relies, in part, on the local synthesis of proteins from localized mRNAs. A strict control of the translation and turnover of these localized mRNAs, both in terms of which proteins are synthesized and when and where they are produced, is a key prerequisite for this process to be synapse-specific. Despite recent advances, the molecular mechanisms mediating this control remain largely elusive. The discovery of P-bodies in neuronal dendrites near synapses and their response to stimuli involved in neuronal plasticity raises the interesting hypothesis that P-bodies might be a component of the cellular machinery that controls neuronal plasticity and thereby processes such as learning and memory.
Topics: Animals; Cytoplasmic Granules; Humans; Neurons; Protein Biosynthesis; RNA Transport; Ribonucleoproteins
PubMed: 19182533
DOI: 10.4161/rna.6948 -
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 -
PLoS Pathogens Jan 2023Kaposi's sarcoma-associated herpesvirus (KSHV) causes the inflammatory and angiogenic endothelial cell neoplasm, Kaposi's sarcoma (KS). We previously demonstrated that...
Kaposi's sarcoma-associated herpesvirus (KSHV) causes the inflammatory and angiogenic endothelial cell neoplasm, Kaposi's sarcoma (KS). We previously demonstrated that the KSHV Kaposin B (KapB) protein promotes inflammation via the disassembly of cytoplasmic ribonucleoprotein granules called processing bodies (PBs). PBs modify gene expression by silencing or degrading labile messenger RNAs (mRNAs), including many transcripts that encode inflammatory or angiogenic proteins associated with KS disease. Although our work implicated PB disassembly as one of the causes of inflammation during KSHV infection, the precise mechanism used by KapB to elicit PB disassembly was unclear. Here we reveal a new connection between the degradative process of autophagy and PB disassembly. We show that both latent KSHV infection and KapB expression enhanced autophagic flux via phosphorylation of the autophagy regulatory protein, Beclin. KapB was necessary for this effect, as infection with a recombinant virus that does not express the KapB protein did not induce Beclin phosphorylation or autophagic flux. Moreover, we showed that PB disassembly mediated by KSHV or KapB, depended on autophagy genes and the selective autophagy receptor NDP52/CALCOCO2 and that the PB scaffolding protein, Pat1b, co-immunoprecipitated with NDP52. These studies reveal a new role for autophagy and the selective autophagy receptor NDP52 in promoting PB turnover and the concomitant synthesis of inflammatory molecules during KSHV infection.
Topics: Humans; Autophagy; Endothelial Cells; Herpesviridae Infections; Herpesvirus 8, Human; Processing Bodies; Sarcoma, Kaposi; Nuclear Proteins
PubMed: 36634147
DOI: 10.1371/journal.ppat.1011080 -
BioRxiv : the Preprint Server For... Jul 2023The intracellular environment is packed with macromolecules of mesoscale size, and this crowded milieu significantly influences cell physiology. When exposed to stress,...
The intracellular environment is packed with macromolecules of mesoscale size, and this crowded milieu significantly influences cell physiology. When exposed to stress, mRNAs released after translational arrest condense with RNA binding proteins, resulting in the formation of membraneless RNA protein (RNP) condensates known as processing bodies (P-bodies) and stress granules (SGs). However, the impact of the assembly of these condensates on the biophysical properties of the crowded cytoplasmic environment remains unclear. Here, we find that upon exposure to stress, polysome collapse and condensation of mRNAs increases mesoscale particle diffusivity in the cytoplasm. Increased mesoscale diffusivity is required for the efficient formation of Q-bodies, membraneless organelles that coordinate degradation of misfolded peptides that accumulate during stress. Additionally, we demonstrate that polysome collapse and stress granule formation has a similar effect in mammalian cells, fluidizing the cytoplasm at the mesoscale. We find that synthetic, light-induced RNA condensation is sufficient to fluidize the cytoplasm, demonstrating a causal effect of RNA condensation. Together, our work reveals a new functional role for stress-induced translation inhibition and formation of RNP condensates in modulating the physical properties of the cytoplasm to effectively respond to stressful conditions.
PubMed: 37398029
DOI: 10.1101/2023.05.30.542963 -
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 -
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 -
Cancer Research Mar 2024Epithelial-mesenchymal transition (EMT) is a fundamental cellular process frequently hijacked by cancer cells to promote tumor progression, especially metastasis. EMT is...
UNLABELLED
Epithelial-mesenchymal transition (EMT) is a fundamental cellular process frequently hijacked by cancer cells to promote tumor progression, especially metastasis. EMT is orchestrated by a complex molecular network acting at different layers of gene regulation. In addition to transcriptional regulation, posttranscriptional mechanisms may also play a role in EMT. Here, we performed a pooled CRISPR screen analyzing the influence of 1,547 RNA-binding proteins on cell motility in colon cancer cells and identified multiple core components of P-bodies (PB) as negative modulators of cancer cell migration. Further experiments demonstrated that PB depletion by silencing DDX6 or EDC4 could activate hallmarks of EMT thereby enhancing cell migration in vitro as well as metastasis formation in vivo. Integrative multiomics analysis revealed that PBs could repress the translation of the EMT driver gene HMGA2, which contributed to PB-meditated regulation of EMT. This mechanism is conserved in other cancer types. Furthermore, endoplasmic reticulum stress was an intrinsic signal that induced PB disassembly and translational derepression of HMGA2. Taken together, this study has identified a function of PBs in the regulation of EMT in cancer.
SIGNIFICANCE
Systematic investigation of the influence of posttranscriptional regulation on cancer cell motility established a connection between P-body-mediated translational control and EMT, which could be therapeutically exploited to attenuate metastasis formation.
Topics: Humans; Processing Bodies; Clustered Regularly Interspaced Short Palindromic Repeats; Early Detection of Cancer; Transcription Factors; Epithelial-Mesenchymal Transition; Colonic Neoplasms; Gene Expression Regulation, Neoplastic; Cell Movement; Cell Line, Tumor; Proteins
PubMed: 38190710
DOI: 10.1158/0008-5472.CAN-23-1693 -
Developmental Cell Sep 2005Processing bodies (P bodies) are discrete cytoplasmic foci to which mRNA is routed for degradation. In mammalian cells, they are also associated with miRNA-induced... (Review)
Review
Processing bodies (P bodies) are discrete cytoplasmic foci to which mRNA is routed for degradation. In mammalian cells, they are also associated with miRNA-induced translational silencing and siRNA-induced mRNA degradation. In a recent issue of Molecular Cell, Ding and coworkers described an argonaute-interacting protein that appears to promote the assembly of P bodies in C. elegans (Ding et al., 2005).
Topics: Animals; Caenorhabditis elegans; Cytoplasmic Structures; Gene Silencing; RNA Interference; RNA, Messenger
PubMed: 16139220
DOI: 10.1016/j.devcel.2005.08.003 -
Journal of Cell Science May 2013In neurons, transport of a subset of mRNAs to subcellular regions and their translation has a role in synaptic plasticity. Recent studies have suggested a control...
In neurons, transport of a subset of mRNAs to subcellular regions and their translation has a role in synaptic plasticity. Recent studies have suggested a control mechanism of this local translation through mRNA compartmentalization or degradation. Here we report that processing bodies (P-bodies), which are involved in mRNA degradation or storage, are transported to dendrites by conventional kinesin (KIF5A) as a motor protein. Neuronal activation induced by depolarization increased the colocalization of P-bodies with PSD-95 in dendrites. This neuronal activity increased the release of Nd1 and Arp2 mRNA from the P-bodies and, consequently, reversed the decrease of F-actin (induced by overexpression of Dcp1a) in the dendrites. Our data suggest that the activity-induced redistribution of P-bodies and mRNA release from P-bodies might have a role in synaptic structural plasticity by altering levels of mRNAs that are involved in the dynamics of the actin cytoskeleton in dendrites.
Topics: Actin Cytoskeleton; Actin-Related Protein 2; Actins; Animals; Dendrites; Inclusion Bodies; Kinesins; Nerve Tissue Proteins; Protein Biosynthesis; RNA, Messenger; Rats
PubMed: 23487039
DOI: 10.1242/jcs.125690 -
Gerontology 2018Cytoplasmic RNA granules represent subcellular compartments that are enriched in protein-bound RNA species. RNA granules are produced by evolutionary divergent... (Review)
Review
Cytoplasmic RNA granules represent subcellular compartments that are enriched in protein-bound RNA species. RNA granules are produced by evolutionary divergent eukaryotes, including yeast, mammals, and plants. The functions of cytoplasmic RNA granules differ widely. They are dictated by the cell type and physiological state, which in turn is determined by intrinsic cell properties and environmental factors. RNA granules provide diverse cellular functions. However, all of the granules contribute to aspects of RNA metabolism. This is exemplified by transcription, RNA storage, silencing, and degradation, as well as mRNP remodeling and regulated translation. Several forms of cytoplasmic mRNA granules are linked to normal physiological processes. For instance, they may coordinate protein synthesis and thereby serve as posttranscriptional "operons". RNA granules also participate in cytoplasmic mRNA trafficking, a process particularly well understood for neurons. Many forms of RNA granules support the preservation of somatic cell performance under normal and stress conditions. On the other hand, severe insults or disease can cause the formation and persistence of RNA granules that contribute to cellular dysfunction, especially in the nervous system. Neurodegeneration and many other diseases linked to RNA granules are associated with aging. Nevertheless, information related to the impact of aging on the various types of RNA granules is presently very limited. This review concentrates on cytoplasmic RNA granules and their role in somatic cell maintenance. We summarize the current knowledge on different types of RNA granules in the cytoplasm, their assembly and function under normal, stress, or disease conditions. Specifically, we discuss processing bodies, neuronal granules, stress granules, and other less characterized cytoplasmic RNA granules. Our focus is primarily on mammalian and yeast models, because they have been critical to unravel the physiological role of various RNA granules. RNA granules in plants and pathogens are briefly described. We conclude our viewpoint by summarizing the emerging concepts for RNA granule biology and the open questions that need to be addressed in future studies.
Topics: Aging; Animals; Cytoplasmic Granules; Homeostasis; Humans; Mitochondria; Neoplasms; Neurons; Parasites; RNA; RNA Processing, Post-Transcriptional; Ribonucleoproteins; Stress, Physiological; Virus Diseases
PubMed: 29847814
DOI: 10.1159/000488759