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Frontiers in Plant Science 2017Regulation of post-transcriptional gene expression on mRNA level in eukaryotic cells includes translocation, translation, translational repression, storage, mRNA decay,... (Review)
Review
Regulation of post-transcriptional gene expression on mRNA level in eukaryotic cells includes translocation, translation, translational repression, storage, mRNA decay, RNA silencing, and nonsense-mediated decay. These processes are associated with various RNA-binding proteins and cytoplasmic ribonucleoprotein complexes many of which are conserved across eukaryotes. Microscopically visible aggregations formed by ribonucleoprotein complexes are termed RNA granules. Stress granules where the translationally inactive mRNAs are stored and processing bodies where mRNA decay may occur present the most studied RNA granule types. Diverse RNP-granules are increasingly being assigned important roles in viral infections. Although the majority of the molecular level studies on the role of RNA granules in viral translation and replication have been conducted in mammalian systems, some studies link also plant virus infection to RNA granules. An increasing body of evidence indicates that plant viruses require components of stress granules and processing bodies for their replication and translation, but how extensively the cellular mRNA regulatory network is utilized by plant viruses has remained largely enigmatic. Antiviral RNA silencing, which is an important regulator of viral RNA stability and expression in plants, is commonly counteracted by viral suppressors of RNA silencing. Some of the RNA silencing suppressors localize to cellular RNA granules and have been proposed to carry out their suppression functions there. Moreover, plant nucleotide-binding leucine-rich repeat protein-mediated virus resistance has been linked to enhanced processing body formation and translational repression of viral RNA. Many interesting questions relate to how the pathways of antiviral RNA silencing leading to viral RNA degradation and/or repression of translation, suppression of RNA silencing and viral RNA translation converge in plants and how different RNA granules and their individual components contribute to these processes. In this review we discuss the roles of cellular RNA regulatory mechanisms and RNA granules in plant virus infection in the light of current knowledge and compare the findings to those made in animal virus studies.
PubMed: 29312371
DOI: 10.3389/fpls.2017.02093 -
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 -
Molecular Plant-microbe Interactions :... Jan 2020RNA granules are dynamic cellular foci that are widely spread in eukaryotic cells and play essential roles in cell growth and development, and immune and stress... (Review)
Review
RNA granules are dynamic cellular foci that are widely spread in eukaryotic cells and play essential roles in cell growth and development, and immune and stress responses. Different types of granules can be distinguished, each with a specific function and playing a role in, for example, RNA transcription, modification, processing, decay, translation, and arrest. By means of communication and exchange of (shared) components, they form a large regulatory network in cells. Viruses have been reported to interact with one or more of these either cytoplasmic or nuclear granules, and act either proviral, to enable and support viral infection and facilitate viral movement, or antiviral, protecting or clearing hosts from viral infection. This review describes an overview and recent progress on cytoplasmic and nuclear RNA granules and their interplay with virus infection, first in animal systems and as a prelude to the status and current developments on plant viruses, which have been less well studied on this thus far.
Topics: Animals; Cytoplasm; Cytoplasmic Granules; Plant Viruses; RNA
PubMed: 31415225
DOI: 10.1094/MPMI-06-19-0161-FI -
Virologica Sinica Apr 2019RNA granules are cytoplasmic, microscopically visible, non-membrane ribo-nucleoprotein structures and are important posttranscriptional regulators in gene expression by... (Review)
Review
RNA granules are cytoplasmic, microscopically visible, non-membrane ribo-nucleoprotein structures and are important posttranscriptional regulators in gene expression by controlling RNA translation and stability. TIA/G3BP/PABP-specific stress granules (SG) and GW182/DCP-specific RNA processing bodies (PB) are two major distinguishable RNA granules in somatic cells and contain various ribosomal subunits, translation factors, scaffold proteins, RNA-binding proteins, RNA decay enzymes and helicases to exclude mRNAs from the cellular active translational pool. Although SG formation is inducible due to cellular stress, PB exist physiologically in every cell. Both RNA granules are important components of the host antiviral defense. Virus infection imposes stress on host cells and thus induces SG formation. However, both RNA and DNA viruses must confront the hostile environment of host innate immunity and apply various strategies to block the formation of SG and PB for their effective infection and multiplication. This review summarizes the current research development in the field and the mechanisms of how individual viruses suppress the formation of host SG and PB for virus production.
Topics: Animals; Cytoplasmic Granules; DNA Viruses; Gene Expression Regulation; Host Microbial Interactions; Humans; Immunity, Innate; Mice; RNA; RNA Viruses; RNA, Messenger; RNA, Viral; Virus Replication
PubMed: 31037644
DOI: 10.1007/s12250-019-00122-3 -
Behavioural Brain Research Feb 2023Parkinson's disease (PD) is a neurodegenerative disease characterized by the progressive loss of dopaminergic neurons in the nigrostriatal pathway. Although the exact... (Review)
Review
Parkinson's disease (PD) is a neurodegenerative disease characterized by the progressive loss of dopaminergic neurons in the nigrostriatal pathway. Although the exact mechanisms underlying PD are still not completely understood, it is well accepted that α-synuclein plays key pathophysiological roles as the main constituent of the cytoplasmic inclusions known as Lewy bodies. Several post-translational modifications (PTMs), such as the best-known phosphorylation, target α-synuclein and are thus implicated in its physiological and pathological functions. In this review, we present (1) an overview of the pathophysiological roles of α-synuclein, (2) a descriptive analysis of α-synuclein PTMs, including phosphorylation, ubiquitination, SUMOylation, acetylation, glycation, truncation, and O-GlcNAcylation, as well as (3) a brief summary on α-synuclein PTMs as potential biomarkers for PD. A better understanding of α-synuclein PTMs is of paramount importance for elucidating the mechanisms underlying PD and can thus be expected to improve early detection and monitoring disease progression, as well as identify promising new therapeutic targets.
Topics: Humans; Parkinson Disease; alpha-Synuclein; Neurodegenerative Diseases; Protein Processing, Post-Translational; Lewy Bodies
PubMed: 36372243
DOI: 10.1016/j.bbr.2022.114204 -
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 -
RNA Biology Jun 2017From their initial identification as 'nucleolar accessory bodies' more than a century ago, the relationship between Cajal bodies and nucleoli has been a subject of... (Review)
Review
From their initial identification as 'nucleolar accessory bodies' more than a century ago, the relationship between Cajal bodies and nucleoli has been a subject of interest and controversy. In this review, we seek to place recent developments in the understanding of the physical and functional relationships between the 2 structures in the context of historical observations. Biophysical models of nuclear body formation, the molecular nature of CB/nucleolus interactions and the increasing list of joint roles for CBs and nucleoli, predominantly in assembling ribonucleoprotein (RNP) complexes, are discussed.
Topics: Animals; Cell Nucleolus; Coiled Bodies; Humans; Mutation; Nuclear Proteins; Protein Binding; RNA Interference; RNA Processing, Post-Transcriptional; RNA, Small Nuclear; Ribonucleoproteins, Small Nuclear; Telomere Homeostasis
PubMed: 27661468
DOI: 10.1080/15476286.2016.1236169 -
Klinische Monatsblatter Fur... Nov 2017Precise knowledge of the neuroanatomy of the visual system including the perception of visual stimuli in the retina, the transmission of visual information to other... (Review)
Review
Precise knowledge of the neuroanatomy of the visual system including the perception of visual stimuli in the retina, the transmission of visual information to other areas of the central nervous system and the processing of visual information, are most important for diagnostics of diseases, which are affecting this system. Such knowledge allows, even after just a clinical examination, already a quite precise localisation of potential lesions. The aim of this article is to illustrate the neuroanatomy of the visual system with the focus on the visual pathway and the processing of visual information. Next to the main visual pathway, also other retinofugal projections are discussed. Domains, which are important for the oculomotor system, are discussed in another article in this edition of the journal.
Topics: Brain Mapping; Dominance, Cerebral; Geniculate Bodies; Humans; Interneurons; Nerve Fibers; Neurons; Optic Nerve; Optic Tract; Retina; Visual Cortex; Visual Fields; Visual Pathways; Visual Perception
PubMed: 29155433
DOI: 10.1055/s-0043-118101 -
World Journal of Microbiology &... Oct 2018Inclusion bodies (IBs) are insoluble aggregates of misfolded protein in Escherichia coli. Against the outdated belief that the production of IBs should be avoided during... (Review)
Review
Inclusion bodies (IBs) are insoluble aggregates of misfolded protein in Escherichia coli. Against the outdated belief that the production of IBs should be avoided during recombinant protein production, quite a number of recombinant products are currently produced as IBs, which are then processed to give correctly folded and soluble product. However, this processing is quite cumbersome comprising IB wash, IB solubilization and refolding. To date, IB processing often happens rather uncontrolled and relies on empiricism rather than sound process understanding. In this mini review we describe current efforts to introduce more monitoring and control in IB processes, focusing on the refolding step, and thus generate process understanding and knowledge.
Topics: Batch Cell Culture Techniques; Escherichia coli; Inclusion Bodies; Protein Folding; Recombinant Proteins; Solubility
PubMed: 30341583
DOI: 10.1007/s11274-018-2541-5