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Current Opinion in Cell Biology Jun 2005Decapping is a central step in eukaryotic mRNA turnover. Recent studies have identified several factors involved in catalysis and regulation of decapping. These include... (Review)
Review
Decapping is a central step in eukaryotic mRNA turnover. Recent studies have identified several factors involved in catalysis and regulation of decapping. These include the following: an mRNA decapping complex containing the proteins Dcp1 and Dcp2; a nucleolar decapping enzyme, X29, involved in the degradation of U8 snoRNA and perhaps of other capped nuclear RNAs; and a decapping 'scavenger' enzyme, DcpS, that hydrolyzes the cap structure resulting from complete 3'-to-5' degradation of mRNAs by the exosome. Several proteins that stimulate mRNA decapping by the Dcp1:Dcp2 complex co-localize with Dcp1 and Dcp2, together with Xrn1, a 5'-to-3' exonuclease, to structures in the cytoplasm called processing bodies. Recent evidence suggests that the processing bodies may constitute specialized cellular compartments of mRNA turnover, which suggests that mRNA and protein localization may be integral to mRNA decay.
Topics: Animals; Cytoplasmic Structures; Endoribonucleases; Humans; Models, Biological; RNA Caps; RNA Stability; RNA-Binding Proteins
PubMed: 15901504
DOI: 10.1016/j.ceb.2005.04.002 -
Molecular and Cellular Biochemistry Apr 2022In recent years, processing bodies (P-bodies) formed by liquid-liquid phase separation, have attracted growing scientific attention due to their involvement in numerous... (Review)
Review
In recent years, processing bodies (P-bodies) formed by liquid-liquid phase separation, have attracted growing scientific attention due to their involvement in numerous cellular activities, including the regulation of mRNAs decay or storage. These cytoplasmic dynamic membraneless granules contain mRNA storage and decay components such as deadenylase and decapping factors. In addition, different mRNA metabolic regulators, including mA readers and gene-mediated miRNA-silencing, are also associated with such P-bodies. Cancerous cells may profit from these mRNA decay shredders by up-regulating the expression level of oncogenes and down-regulating tumor suppressor genes. The main challenges of cancer treatment are drug resistance, metastasis, and cancer relapse likely associated with cancer stem cells, heterogeneity, and plasticity features of different tumors. The mRNA metabolic regulators based on P-bodies play a great role in cancer development and progression. The dysregulation of P-bodies mediators affects mRNA metabolism. However, less is known about the relationship between P-bodies mediators and cancerous behavior. The current review summarizes the recent studies on P-bodies mediators, their contribution to tumor development, and their potential in the clinical setting, particularly highlighting the P-bodies as potential drug-carriers such as exosomes to anticancer in the future.
Topics: Humans; Neoplasms; Processing Bodies; RNA Stability; RNA, Messenger; RNA, Neoplasm
PubMed: 35089528
DOI: 10.1007/s11010-022-04359-7 -
Progress in Molecular Biology and... 2009Stress necessitates rapid reprogramming of translation in order to facilitate an adaptive response and promote survival. Cytoplasmic stress granules (SGs) and processing... (Review)
Review
Stress necessitates rapid reprogramming of translation in order to facilitate an adaptive response and promote survival. Cytoplasmic stress granules (SGs) and processing bodies (PBs) are dynamic structures that form in response to stress-induced translational arrest. PBs are linked to mRNA silencing and decay, while SGs are more closely linked to translation and the sorting of specific mRNAs for different fates. While they share some components and can interact physically, SGs and PBs are regulated independently, house separate functions, and contain unique markers. SG formation is associated with numerous disease states, and the expanding list of SG-associated proteins integrates SG formation with other processes such as transcription, splicing, and survival. Growing evidence suggests that SG assembly is initiated by translational arrest, and mediates cross talk with many other signaling pathways.
Topics: Animals; Cytoplasmic Granules; Cytoplasmic Structures; Disease; Humans; Models, Biological; Protein Biosynthesis; Saccharomyces cerevisiae
PubMed: 20374741
DOI: 10.1016/S1877-1173(09)90004-7 -
Nucleic Acids Research Sep 2023Two prominent cytoplasmic RNA granules, ubiquitous RNA-processing bodies (PB) and inducible stress granules (SG), regulate mRNA translation and are intimately related....
Two prominent cytoplasmic RNA granules, ubiquitous RNA-processing bodies (PB) and inducible stress granules (SG), regulate mRNA translation and are intimately related. In this study, we found that arsenite (ARS)-induced SG formed in a stepwise process is topologically and mechanically linked to PB. Two essential PB components, GW182 and DDX6, are repurposed under stress to play direct but distinguishable roles in SG biogenesis. By providing scaffolding activities, GW182 promotes the aggregation of SG components to form SG bodies. DEAD-box helicase DDX6 is also essential for the proper assembly and separation of PB from SG. DDX6 deficiency results in the formation of irregularly shaped 'hybrid' PB/SG granules with accumulated components of both PB and SG. Wild-type DDX6, but not its helicase mutant E247A, can rescue the separation of PB from SG in DDX6KO cells, indicating a requirement of DDX6 helicase activity for this process. DDX6 activity in biogenesis of both PB and SG in the cells under stress is further modulated by its interaction with two protein partners, CNOT1 and 4E-T, of which knockdown affects the formation of both PB and also SG. Together, these data highlight a new functional paradigm between PB and SG biogenesis during the stress.
Topics: Cytoplasmic Granules; DEAD-box RNA Helicases; Processing Bodies; RNA; RNA Processing, Post-Transcriptional; Stress Granules; Humans; Cell Line
PubMed: 37427791
DOI: 10.1093/nar/gkad585 -
Current Opinion in Genetics &... Apr 2008In diverse eukaryotes, micro-RNAs (miRNAs) and small interfering RNAs (siRNAs) regulate important processes that include mRNA inactivation, viral defense, chromatin... (Review)
Review
In diverse eukaryotes, micro-RNAs (miRNAs) and small interfering RNAs (siRNAs) regulate important processes that include mRNA inactivation, viral defense, chromatin modification, and transposon silencing. Recently, nucleolus-associated Cajal bodies in plants have been implicated as sites of siRNA and miRNA biogenesis, whereas in animals siRNA and miRNA dicing occurs in the cytoplasm. The plant nucleolus also contains proteins of the nonsense-mediated mRNA decay pathway that in animals are found associated with cytoplasmic processing bodies (P-bodies). P-bodies also function in the degradation of mRNAs subjected to miRNA and siRNA targeting. Collectively, these observations suggest interesting variations in the way siRNAs and miRNAs can accomplish their similar functions in plants and animals.
Topics: Animals; Cell Cycle Proteins; Cell Nucleolus; Coiled Bodies; Humans; MicroRNAs; RNA, Small Interfering; Ribonuclease III
PubMed: 18337083
DOI: 10.1016/j.gde.2008.01.008 -
Biochimica Et Biophysica Acta Jul 2015Cancer cells are exposed to adverse conditions in the tumor microenvironment, and utilize post-transcriptional control mechanisms to re-program gene expression in ways... (Review)
Review
Cancer cells are exposed to adverse conditions in the tumor microenvironment, and utilize post-transcriptional control mechanisms to re-program gene expression in ways that enhance cell survival. Stress granules and processing bodies are RNA-containing granules that contribute to this process by modulating cellular signaling pathways, metabolic machinery, and stress response programs. This review examines evidence implicating RNA granules in the pathogenesis of cancer and discusses their potential as targets for anticancer therapies. This article is part of a Special Issue entitled: Translation and Cancer.
Topics: Animals; Cytoplasmic Granules; Gene Expression Regulation, Neoplastic; Humans; Neoplasms; RNA, Neoplasm
PubMed: 25482014
DOI: 10.1016/j.bbagrm.2014.11.009 -
Wiley Interdisciplinary Reviews. RNA Nov 2020In bacteria, mRNA decay is controlled by megadalton scale macromolecular assemblies called, "RNA degradosomes," composed of nucleases and other RNA decay associated... (Review)
Review
In bacteria, mRNA decay is controlled by megadalton scale macromolecular assemblies called, "RNA degradosomes," composed of nucleases and other RNA decay associated proteins. Recent advances in bacterial cell biology have shown that RNA degradosomes can assemble into phase-separated structures, termed bacterial ribonucleoprotein bodies (BR-bodies), with many analogous properties to eukaryotic processing bodies and stress granules. This review will highlight the functional role that BR-bodies play in the mRNA decay process through its organization into a membraneless organelle in the bacterial cytoplasm. This review will also highlight the phylogenetic distribution of BR-bodies across bacterial species, which suggests that these phase-separated structures are broadly distributed across bacteria, and in evolutionarily related mitochondria and chloroplasts. This article is categorized under: RNA Turnover and Surveillance > Turnover/Surveillance Mechanisms RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes RNA Export and Localization > RNA Localization RNA Turnover and Surveillance > Regulation of RNA Stability.
Topics: Bacteria; Chloroplasts; Mitochondria; RNA, Messenger; Ribonucleoproteins
PubMed: 32445438
DOI: 10.1002/wrna.1599 -
The Plant Cell Sep 2023Flowering is the transition from vegetative to reproductive growth and is critical for plant adaptation and reproduction. FLOWERING LOCUS C (FLC) plays a central role in...
Flowering is the transition from vegetative to reproductive growth and is critical for plant adaptation and reproduction. FLOWERING LOCUS C (FLC) plays a central role in flowering time control, and dissecting its regulation mechanism provides essential information for crop improvement. Here, we report that DECAPPING5 (DCP5), a component of processing bodies (P-bodies), regulates FLC transcription and flowering time in Arabidopsis (Arabidopsis thaliana). DCP5 and its interacting partner SISTER OF FCA (SSF) undergo liquid-liquid phase separation (LLPS) that is mediated by their prion-like domains (PrDs). Enhancing or attenuating the LLPS of both proteins using transgenic methods greatly affects their ability to regulate FLC and flowering time. DCP5 regulates FLC transcription by modulating RNA polymerase II enrichment at the FLC locus. DCP5 requires SSF for FLC regulation, and loss of SSF or its PrD disrupts DCP5 function. Our results reveal that DCP5 interacts with SSF, and the nuclear DCP5-SSF complex regulates FLC expression at the transcriptional level.
Topics: Arabidopsis; Arabidopsis Proteins; Co-Repressor Proteins; Flowers; Gene Expression Regulation, Plant; MADS Domain Proteins; Mutation; Processing Bodies; Reproduction
PubMed: 37220754
DOI: 10.1093/plcell/koad151 -
Molecular and Cellular Biology Oct 2021Processing bodies (PBs) are ribonucleoprotein granules important for cytokine mRNA decay that are targeted for disassembly by many viruses. Kaposi's sarcoma-associated...
Processing bodies (PBs) are ribonucleoprotein granules important for cytokine mRNA decay that are targeted for disassembly by many viruses. Kaposi's sarcoma-associated herpesvirus is the etiological agent of the inflammatory endothelial cancer, Kaposi's sarcoma, and a PB-regulating virus. The virus encodes kaposin B (KapB), which induces actin stress fibers (SFs) and cell spindling as well as PB disassembly. We now show that KapB-mediated PB disassembly requires actin rearrangements, RhoA effectors, and the mechanoresponsive transcription activator, YAP. Moreover, ectopic expression of active YAP or exposure of ECs to mechanical forces caused PB disassembly in the absence of KapB. We propose that the viral protein KapB activates a mechanoresponsive signaling axis and links changes in cell shape and cytoskeletal structures to enhanced inflammatory molecule expression using PB disassembly. Our work implies that cytoskeletal changes in other pathologies may similarly impact the inflammatory environment.
Topics: Actin Cytoskeleton; Actomyosin; Cell Shape; Cell Transformation, Neoplastic; Gene Expression Regulation; Herpesvirus 8, Human; Host Microbial Interactions; Humans; Mechanotransduction, Cellular; Processing Bodies; Sarcoma, Kaposi; Signal Transduction; Viral Proteins; Virus Replication; YAP-Signaling Proteins; rhoA GTP-Binding Protein
PubMed: 34516278
DOI: 10.1128/MCB.00399-21 -
RNA (New York, N.Y.) Jul 2009Nonsense-mediated mRNA decay (NMD) is a eukaryotic quality-control mechanism that recognizes and degrades mRNAs with premature termination codons (PTCs). In yeast,...
Nonsense-mediated mRNA decay (NMD) is a eukaryotic quality-control mechanism that recognizes and degrades mRNAs with premature termination codons (PTCs). In yeast, PTC-containing mRNAs are targeted to processing bodies (P-bodies), and yeast strains expressing an ATPase defective Upf1p mutant accumulate P-bodies. Here we show that in human cells, an ATPase-deficient UPF1 mutant and a fraction of UPF2 and UPF3b accumulate in cytoplasmic foci that co-localize with P-bodies. Depletion of the P-body component Ge-1, which prevents formation of microscopically detectable P-bodies, also impairs the localization of mutant UPF1, UPF2, and UPF3b in cytoplasmic foci. However, the accumulation of the ATPase-deficient UPF1 mutant in P-bodies is independent of UPF2, UPF3b, or SMG1, and the ATPase-deficient UPF1 mutant can localize into the P-bodies independent of its phosphorylation status. Most importantly, disruption of P-bodies by depletion of Ge-1 affects neither the mRNA levels of PTC-containing reporter genes nor endogenous NMD substrates. Consistent with the recently reported decapping-independent SMG6-mediated endonucleolytic decay of human nonsense mRNAs, our results imply that microscopically detectable P-bodies are not required for mammalian NMD.
Topics: Codon, Nonsense; Cytoplasmic Structures; HeLa Cells; Humans; Immunoblotting; Immunoenzyme Techniques; Mutation; Phosphatidylinositol 3-Kinases; Phosphoinositide-3 Kinase Inhibitors; Phosphorylation; Protein Serine-Threonine Kinases; RNA Helicases; RNA Stability; RNA, Messenger; RNA, Small Interfering; RNA-Binding Proteins; Reverse Transcriptase Polymerase Chain Reaction; Trans-Activators; Transcription Factors
PubMed: 19474145
DOI: 10.1261/rna.1672509