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Wiley Interdisciplinary Reviews. RNA May 2019In response to stress, cells must quickly reprogram gene expression to adapt and survive. This is achieved in part by altering levels of mRNAs and their translation into... (Review)
Review
In response to stress, cells must quickly reprogram gene expression to adapt and survive. This is achieved in part by altering levels of mRNAs and their translation into proteins. Recently, the formation of two stress-induced messenger ribonucleoprotein (mRNP) assemblies named stress granules and processing bodies has been postulated to directly impact gene expression during stress. These assemblies sequester and concentrate specific proteins and RNAs away from the larger cytoplasm during stress, thereby providing a layer of posttranscriptional gene regulation with the potential to directly impact mRNA levels, protein translation, and cell survival. The function of these granules has generally been ascribed either by the protein components concentrated into them or, more broadly, by global changes that occur during stress. Recent proteome- and transcriptome-wide studies have provided a more complete view of stress-induced mRNP granule composition in varied cell types and stress conditions. However, direct measurements of the phenotypic and functional consequences of stress granule and processing body formation are lacking. This leaves our understanding of their roles during stress incomplete. Continued study into the function of these granules will be an important part in elucidating how cells respond to and survive stressful environmental changes. This article is categorized under: Translation > Translation Regulation RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes RNA Export and Localization > RNA Localization.
Topics: Cytoplasmic Granules; Eukaryotic Cells; Protein Biosynthesis; RNA Processing, Post-Transcriptional; Ribonucleoproteins; Stress, Physiological
PubMed: 30793528
DOI: 10.1002/wrna.1524 -
Neuroscience and Biobehavioral Reviews May 2020The human "person" is a common percept we encounter. Research on person perception has been focused either on face or body perception-with less attention paid to whole... (Review)
Review
The human "person" is a common percept we encounter. Research on person perception has been focused either on face or body perception-with less attention paid to whole person perception. We review psychological and neuroscience studies aimed at understanding how face and body processing operate in concert to support intact person perception. We address this question considering: a.) the task to be accomplished (identification, emotion processing, detection), b.) the neural stage of processing (early/late visual mechanisms), and c.) the relevant brain regions for face/body/person processing. From the psychological perspective, we conclude that the integration of faces and bodies is mediated by the goal of the processing (e.g., emotion analysis, identification, etc.). From the neural perspective, we propose a hierarchical functional neural architecture of face-body integration that retains a degree of separation between the dorsal and ventral visual streams. We argue for two centers of integration: a ventral semantic integration hub that is the result of progressive, posterior-to-anterior, face-body integration; and a social agent integration hub in the dorsal stream STS.
Topics: Brain; Facial Recognition; Humans; Pattern Recognition, Visual; Social Perception
PubMed: 32088346
DOI: 10.1016/j.neubiorev.2020.02.021 -
Current Opinion in Cell Biology Jun 2017The cell nucleus contains a number of different dynamic bodies that are variously composed of proteins and generally, but not always, specific RNA molecules. Recent... (Review)
Review
The cell nucleus contains a number of different dynamic bodies that are variously composed of proteins and generally, but not always, specific RNA molecules. Recent studies have revealed new understanding about nuclear body formation and function in different aspects of nuclear metabolism. Here, we focus on findings describing the role of nuclear bodies in the biogenesis of specific ribonucleoprotein complexes, processing of key mRNAs, and subnuclear sequestration of protein factors. We highlight how nuclear bodies are involved in stress responses, innate immunity and tumorigenesis. We further review organization of nuclear bodies and principles that govern their assembly, highlighting the pivotal role of scaffolding noncoding RNAs, and liquid-liquid phase separation, which are transforming our picture of nuclear body formation.
Topics: Animals; Cell Nucleus; Humans; Intranuclear Inclusion Bodies; Nuclear Proteins; RNA, Untranslated
PubMed: 28577509
DOI: 10.1016/j.ceb.2017.05.001 -
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 -
Trends in Cancer Oct 2021Stress granules (SGs) and processing bodies (P-bodies) are membraneless cytoplasmic condensates of ribonucleoproteins (RNPs). They both regulate RNA fate under... (Review)
Review
Stress granules (SGs) and processing bodies (P-bodies) are membraneless cytoplasmic condensates of ribonucleoproteins (RNPs). They both regulate RNA fate under physiological and pathological conditions, and are thereby involved in the regulation and maintenance of cellular integrity. During tumorigenesis, cancer cells use these granules to thrive, to adapt to the harsh conditions of the tumor microenvironment (TME), and to protect themselves from anticancer treatments. This ability to provide multiple outcomes not only makes RNP granules promising targets for cancer therapy but also emphasizes the need for more knowledge about the biology of these granules to achieve clinical use. In this review we focus on the role of RNP granules in cancer, and on how their composition and regulation might be used to elaborate therapeutic strategies.
Topics: Cytoplasmic Granules; Cytoplasmic Ribonucleoprotein Granules; Neoplasms; Processing Bodies; Ribonucleoproteins; Stress Granules
PubMed: 34144941
DOI: 10.1016/j.trecan.2021.05.006 -
Biochemistry May 2018Nuclear bodies are RNA-rich membraneless organelles in the cell nucleus that concentrate specific sets of nuclear proteins and RNA-protein complexes. Nuclear bodies such... (Review)
Review
Nuclear bodies are RNA-rich membraneless organelles in the cell nucleus that concentrate specific sets of nuclear proteins and RNA-protein complexes. Nuclear bodies such as the nucleolus, Cajal body (CB), and the histone locus body (HLB) concentrate factors required for nuclear steps of RNA processing. Formation of these nuclear bodies occurs on genomic loci and is frequently associated with active sites of transcription. Whether nuclear body formation is dependent on a particular gene element, an active process such as transcription, or the nascent RNA present at gene loci is a topic of debate. Recently, this question has been addressed through studies in model organisms and their embryos. The switch from maternally provided RNA and protein to zygotic gene products in early embryos has been well characterized in a variety of organisms. This process, termed maternal-to-zygotic transition, provides an excellent model for studying formation of nuclear bodies before, during, and after the transcriptional activation of the zygotic genome. Here, we review findings in embryos that reveal key principles in the study of the formation and function of nucleoli, CBs, and HLBs. We propose that while particular gene elements may contribute to formation of these nuclear bodies, active transcription promotes maturation of nuclear bodies and efficient RNA processing within them.
Topics: Cell Nucleolus; Coiled Bodies; Embryonic Development; Genome; Histones; Humans; Nuclear Proteins; RNA; RNA Processing, Post-Transcriptional; RNA Splicing; Ribonucleoproteins, Small Nuclear; Transcription, Genetic
PubMed: 29473743
DOI: 10.1021/acs.biochem.7b01262 -
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 -
Advances in Experimental Medicine and... 2019In recent years, cytoplasmic RNA granules, which are micron-sized membrane-less entities formed by phase separation, have progressively gained recognition as essential... (Review)
Review
In recent years, cytoplasmic RNA granules, which are micron-sized membrane-less entities formed by phase separation, have progressively gained recognition as essential constituents of neuronal RNA metabolism. Stress granules form under adverse growth conditions in order to protect nontranslating mRNA, shift translation toward the production of prosurvival factors, as well as potentially serve as hubs for intracellular signaling. In contrast, processing bodies play a role in RNA degradation in both stressed and homeostatic conditions. Lastly, transport granules permit, as their name indicates, the transport of mRNA within neurons. All of these granule subtypes are required for proper neuronal function; thus, impairments in their regulation and/or composition are expected to be deleterious. Here, we review these cytoplasmic RNA granule subtypes and discuss how they have been implicated in some neurodegenerative diseases.
Topics: Cytoplasmic Granules; Humans; Neurodegenerative Diseases; RNA, Messenger
PubMed: 31811636
DOI: 10.1007/978-3-030-31434-7_8 -
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