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RNA Biology 2015Initially identified as a marker of coiled bodies (now Cajal bodies or CBs), the protein coilin was discovered a quarter of century ago. Coilin is now known to scaffold... (Review)
Review
Initially identified as a marker of coiled bodies (now Cajal bodies or CBs), the protein coilin was discovered a quarter of century ago. Coilin is now known to scaffold the CB, but its structure and function are poorly understood. Nearly devoid of predicted structural motifs, coilin has numerous reported molecular interactions that must underlie its role in the formation and function of CBs. In this review, we summarize what we have learned in the past 25 years about coilin's structure, post-transcriptional modifications, and interactions with RNA and proteins. We show that genes with homology to human coilin are found in primitive metazoans and comment on differences among model organisms. Coilin's function in Cajal body formation and RNP metabolism will be discussed in the light of these developments.
Topics: Animals; Coiled Bodies; History, 20th Century; History, 21st Century; Humans; Nuclear Proteins; Protein Processing, Post-Translational
PubMed: 25970135
DOI: 10.1080/15476286.2015.1034923 -
Journal of Virology May 2016During infection, positive-strand RNA viruses subvert cellular machinery involved in RNA metabolism to translate viral proteins and replicate viral genomes to avoid or... (Review)
Review
During infection, positive-strand RNA viruses subvert cellular machinery involved in RNA metabolism to translate viral proteins and replicate viral genomes to avoid or disable the host defense mechanisms. Cytoplasmic RNA granules modulate the stabilities of cellular and viral RNAs. Understanding how hepatitis C virus and other flaviviruses interact with the host machinery required for protein synthesis, localization, and degradation of mRNAs is important for elucidating how these processes occur in both virus-infected and uninfected cells.
Topics: Cytoplasmic Granules; Genome, Viral; Hepacivirus; Host-Pathogen Interactions; Humans; MicroRNAs; RNA, Messenger; RNA, Small Interfering; RNA, Viral
PubMed: 26937026
DOI: 10.1128/JVI.03056-15 -
Neural Plasticity 2016The effect of deafness on sensory abilities has been the topic of extensive investigation over the past decades. These investigations have mostly focused on visual... (Review)
Review
The effect of deafness on sensory abilities has been the topic of extensive investigation over the past decades. These investigations have mostly focused on visual capacities. We are only now starting to investigate how the deaf experience their own bodies and body-related abilities. Indeed, a growing corpus of research suggests that auditory input could play an important role in body-related processing. Deafness could therefore disturb such processes. It has also been suggested that many unexplained daily difficulties experienced by the deaf could be related to deficits in this underexplored field. In the present review, we propose an overview of the current state of knowledge on the effects of deafness on body-related processing.
Topics: Body Image; Deafness; Humans; Motor Activity; Neuronal Plasticity; Posture; Touch Perception
PubMed: 26881115
DOI: 10.1155/2016/5260671 -
Visual Neuroscience Jan 2017The thalamocortical (TC) relay neuron of the dorsoLateral Geniculate Nucleus (dLGN) has borne its imprecise label for many decades in spite of strong evidence that its... (Review)
Review
The thalamocortical (TC) relay neuron of the dorsoLateral Geniculate Nucleus (dLGN) has borne its imprecise label for many decades in spite of strong evidence that its role in visual processing transcends the implied simplicity of the term "relay". The retinogeniculate synapse is the site of communication between a retinal ganglion cell and a TC neuron of the dLGN. Activation of retinal fibers in the optic tract causes reliable, rapid, and robust postsynaptic potentials that drive postsynaptics spikes in a TC neuron. Cortical and subcortical modulatory systems have been known for decades to regulate retinogeniculate transmission. The dynamic properties that the retinogeniculate synapse itself exhibits during and after developmental refinement further enrich the role of the dLGN in the transmission of the retinal signal. Here we consider the structural and functional substrates for retinogeniculate synaptic transmission and plasticity, and reflect on how the complexity of the retinogeniculate synapse imparts a novel dynamic and influential capacity to subcortical processing of visual information.
Topics: Animals; Excitatory Postsynaptic Potentials; Geniculate Bodies; Patch-Clamp Techniques; Retinal Ganglion Cells; Synapses; Synaptic Transmission; Visual Pathways
PubMed: 28965513
DOI: 10.1017/S0952523817000104 -
Cell Reports Oct 2023Bacterial ribonucleoprotein bodies (BR-bodies) are non-membrane-bound structures that facilitate mRNA decay by concentrating mRNA substrates with RNase E and the...
Bacterial ribonucleoprotein bodies (BR-bodies) are non-membrane-bound structures that facilitate mRNA decay by concentrating mRNA substrates with RNase E and the associated RNA degradosome machinery. However, the full complement of proteins enriched in BR-bodies has not been defined. Here, we define the protein components of BR-bodies through enrichment of the bodies followed by mass spectrometry-based proteomic analysis. We find 111 BR-body-enriched proteins showing that BR-bodies are more complex than previously assumed. We identify five BR-body-enriched proteins that undergo RNA-dependent phase separation in vitro with a complex network of condensate mixing. We observe that some RNP condensates co-assemble with preferred directionality, suggesting that RNA may be trafficked through RNP condensates in an ordered manner to facilitate mRNA processing/decay, and that some BR-body-associated proteins have the capacity to dissolve the condensate. Altogether, these results suggest that a complex network of protein-protein and protein-RNA interactions controls BR-body phase separation and RNA processing.
Topics: RNA; Proteome; Proteomics; Ribonucleoproteins; RNA, Messenger
PubMed: 37815915
DOI: 10.1016/j.celrep.2023.113229 -
The EMBO Journal Nov 2023Deadenylation-dependent mRNA decapping and decay is the major cytoplasmic mRNA turnover pathway in eukaryotes. Many mRNA decapping and decay factors are associated with...
Deadenylation-dependent mRNA decapping and decay is the major cytoplasmic mRNA turnover pathway in eukaryotes. Many mRNA decapping and decay factors are associated with each other via protein-protein interaction motifs. For example, the decapping enzyme DCP2 and the 5'-3' exonuclease XRN1 interact with the enhancer of mRNA-decapping protein 4 (EDC4), a large scaffold that has been reported to stimulate mRNA decapping. mRNA decapping and decay factors are also found in processing bodies (P-bodies), evolutionarily conserved ribonucleoprotein granules that are often enriched with mRNAs targeted for decay, yet paradoxically are not required for mRNA decay to occur. Here, we show that disrupting the EDC4-XRN1 interaction or altering their stoichiometry inhibits mRNA decapping, with microRNA-targeted mRNAs being stabilized in a translationally repressed state. Importantly, we demonstrate that this concomitantly leads to larger P-bodies that are responsible for preventing mRNA decapping. Finally, we demonstrate that P-bodies support cell viability and prevent stress granule formation when XRN1 is limiting. Taken together, these data demonstrate that the interaction between XRN1 and EDC4 regulates P-body dynamics to properly coordinate mRNA decapping with 5'-3' decay in human cells.
Topics: Humans; RNA, Messenger; Processing Bodies; Endoribonucleases; Proteins; Eukaryota; RNA Stability; Exoribonucleases; Microtubule-Associated Proteins
PubMed: 37621215
DOI: 10.15252/embj.2023113933 -
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 -
Frontiers in Cellular and Infection... 2018In eukaryotic cells, the life cycle of mRNA molecules is modulated in response to environmental signals and cell-cell communication in order to support cellular... (Review)
Review
In eukaryotic cells, the life cycle of mRNA molecules is modulated in response to environmental signals and cell-cell communication in order to support cellular homeostasis. Capping, splicing and polyadenylation in the nucleus lead to the formation of transcripts that are suitable for translation in cytoplasm, until mRNA decay occurs in P-bodies. Although pre-mRNA processing and degradation mechanisms have usually been studied separately, they occur simultaneously and in a coordinated manner through protein-protein interactions, maintaining the integrity of gene expression. In the past few years, the availability of the genome sequence of , the protozoan parasite responsible for human amoebiasis, coupled to the development of the so-called "omics" technologies provided new opportunities for the study of mRNA processing and turnover in this pathogen. Here, we review the current knowledge about the molecular basis for splicing, 3' end formation and mRNA degradation in amoeba, which suggest the conservation of events related to mRNA life throughout evolution. We also present the functional characterization of some key proteins and describe some interactions that indicate the relevance of cooperative regulatory events for gene expression in this human parasite.
Topics: Amebiasis; Animals; Entamoeba histolytica; Evolution, Molecular; Humans; Polyadenylation; Protozoan Proteins; RNA Precursors; RNA Splicing; RNA Stability; RNA, Messenger
PubMed: 29971219
DOI: 10.3389/fcimb.2018.00199