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Plants (Basel, Switzerland) Feb 2022Based on prior knowledge and with the support of new methodology, solid progress in the understanding of seed life has taken place over the few last years. This update... (Review)
Review
Based on prior knowledge and with the support of new methodology, solid progress in the understanding of seed life has taken place over the few last years. This update reflects recent advances in three key traits of seed life (i.e., preharvest sprouting, genomic imprinting, and stored-mRNA). The first breakthrough refers to cloning of the mitogen-activated protein kinase-kinase 3 (MKK3) gene in barley and wheat. MKK3, in cooperation with ABA signaling, controls seed dormancy. This advance has been determinant in producing improved varieties that are resistant to preharvest sprouting. The second advance concerns to uniparental gene expression (i.e., imprinting). Genomic imprinting primarily occurs in the endosperm. Although great advances have taken place in the last decade, there is still a long way to go to complete the puzzle regarding the role of genomic imprinting in seed development. This trait is probably one of the most important epigenetic facets of developing endosperm. An example of imprinting regulation is polycomb repressive complex 2 (PRC2). The mechanism of PRC2 recruitment to target endosperm with specific genes is, at present, robustly studied. Further progress in the knowledge of recruitment of PRC2 epigenetic machinery is considered in this review. The third breakthrough referred to in this update involves stored mRNA. The role of the population of this mRNA in germination is far from known. Its relations to seed aging, processing bodies (P bodies), and RNA binding proteins (RBPs), and how the stored mRNA is targeted to monosomes, are aspects considered here. Perhaps this third trait is the one that will require greater experimental dedication in the future. In order to make progress, herein are included some questions that are needed to be answered.
PubMed: 35214823
DOI: 10.3390/plants11040490 -
Nature Communications Jul 2022Insulin is a potent inducer of mRNA transcription and translation, contributing to metabolic regulation. Insulin has also been suggested to regulate mRNA stability...
Insulin is a potent inducer of mRNA transcription and translation, contributing to metabolic regulation. Insulin has also been suggested to regulate mRNA stability through the processing body (P-body) molecular machinery. However, whether and how insulin regulates mRNA stability via P-bodies is not clear. Here we show that the E3-ligase TRIM24 is a critical factor linking insulin signalling to P-bodies. Upon insulin stimulation, protein kinase B (PKB, also known as Akt) phosphorylates TRIM24 and stimulates its shuttling from the nucleus into the cytoplasm. TRIM24 interacts with several critical components of P-bodies in the cytoplasm, promoting their polyubiquitylation, which consequently stabilises Pparγ mRNA. Inactivation of TRIM24 E3-ligase activity or prevention of its phosphorylation via knockin mutations in mice promotes hepatic Pparγ degradation via P-bodies. Consequently, both knockin mutations alleviate hepatosteatosis in mice fed on a high-fat diet. Our results demonstrate the critical role of TRIM24 in linking insulin signalling to P-bodies and have therapeutic implications for the treatment of hepatosteatosis.
Topics: Animals; Insulin; Mice; Nuclear Proteins; PPAR gamma; Processing Bodies; RNA, Messenger; Transcription Factors; Ubiquitin-Protein Ligases
PubMed: 35803934
DOI: 10.1038/s41467-022-31735-0 -
Frontiers in Microbiology 2021RNA granules are cytoplasmic, non-membranous ribonucleoprotein compartments that form ubiquitously and are often referred to as foci for post-transcriptional gene... (Review)
Review
RNA granules are cytoplasmic, non-membranous ribonucleoprotein compartments that form ubiquitously and are often referred to as foci for post-transcriptional gene regulation. Recent research on RNA processing bodies (PB) and stress granules (SG) has shown wide implications of these cytoplasmic RNA granules and their components in suppression of RNA translation as host intracellular innate immunity against infecting viruses. Many RNA viruses either counteract or co-opt these RNA granules; however, many fundamental questions about DNA viruses with respect to their interaction with these two RNA granules remain elusive. Kaposi's sarcoma-associated herpesvirus (KSHV), a tumor-causing DNA virus, exhibits two distinct phases of infection and encodes ∼90 viral gene products during the lytic phase of infection compared to only a few (∼5) during the latent phase. Thus, productive KSHV infection relies heavily on the host cell translational machinery, which often links to the formation of PB and SG. One major question is how KSHV counteracts the hostile environment of RNA granules for its productive infection. Recent studies demonstrated that KSHV copes with the translational suppression by cellular RNA granules, PB and SG, by expressing ORF57, a viral RNA-binding protein, during KSHV lytic infection. ORF57 interacts with Ago2 and GW182, two major components of PB, and prevents the scaffolding activity of GW182 at the initial stage of PB formation in the infected cells. ORF57 also interacts with protein kinase R (PKR) and PKR-activating protein (PACT) to block PKR dimerization and kinase activation, and thus inhibits eIF2α phosphorylation and SG formation. The homologous immediate-early regulatory protein ICP27 of herpes simplex virus type 1 (HSV-1), but not the EB2 protein of Epstein-Barr virus (EBV), shares this conserved inhibitory function with KSHV ORF57 on PB and SG. Through KSHV ORF57 studies, we have learned much about how a DNA virus in the infected cells is equipped to evade host antiviral immunity for its replication and productive infection. KSHV ORF57 would be an excellent viral target for development of anti-KSHV-specific therapy.
PubMed: 35069491
DOI: 10.3389/fmicb.2021.794431 -
Traffic (Copenhagen, Denmark) Sep 2019In cells at steady state, two forms of cell compartmentalization coexist: membrane-bound organelles and phase-separated membraneless organelles that are present in both... (Review)
Review
In cells at steady state, two forms of cell compartmentalization coexist: membrane-bound organelles and phase-separated membraneless organelles that are present in both the nucleus and the cytoplasm. Strikingly, cellular stress is a strong inducer of the reversible membraneless compartments referred to as stress assemblies. Stress assemblies play key roles in survival during cell stress and in thriving of cells upon stress relief. The two best studied stress assemblies are the RNA-based processing-bodies (P-bodies) and stress granules that form in response to oxidative, endoplasmic reticulum (ER), osmotic and nutrient stress as well as many others. Interestingly, P-bodies and stress granules are heterogeneous with respect to both the pathways that lead to their formation and their protein and RNA content. Furthermore, in yeast and Drosophila, nutrient stress also leads to the formation of many other types of prosurvival cytoplasmic stress assemblies, such as metabolic enzymes foci, proteasome storage granules, EIF2B bodies, U-bodies and Sec bodies, some of which are not RNA-based. Nutrient stress leads to a drop in cytoplasmic pH, which combined with posttranslational modifications of granule contents, induces phase separation.
Topics: Animals; Cytoplasmic Granules; Humans; Proteasome Endopeptidase Complex; Ribonucleoproteins; Stress, Physiological; Yeasts
PubMed: 31152627
DOI: 10.1111/tra.12669 -
BMC Molecular Biology Aug 2016Eukaryotic translation initiation factor 4E (eIF4E) plays a pivotal role in the control of cap-dependent translation initiation, modulates the fate of specific mRNAs,...
BACKGROUND
Eukaryotic translation initiation factor 4E (eIF4E) plays a pivotal role in the control of cap-dependent translation initiation, modulates the fate of specific mRNAs, occurs in processing bodies (PBs) and is required for formation of stress granules (SGs). In this study, we focused on the subcellular localization of a representative compendium of eIF4E protein isoforms, particularly on the less studied members of the human eIF4E protein family, eIF4E2 and eIF4E3.
RESULTS
We showed that unlike eIF4E1, its less studied isoform eIF4E3_A, encoded by human chromosome 3, localized to stress granules but not PBs upon both heat shock and arsenite stress. Furthermore, we found that eIF4E3_A interacts with human translation initiation factors eIF4G1, eIF4G3 and PABP1 in vivo and sediments into the same fractions as canonical eIF4E1 during polysome analysis in sucrose gradients. Contrary to this finding, the truncated human eIF4E3 isoform, eIF4E3_B, showed no localization to SGs and no binding to eIF4G. We also highlighted that eIF4E2 may exhibit distinct functions under different stresses as it readily localizes to P-bodies during arsenite and heat stresses, whereas it is redirected to stress granules only upon heat shock. We extended our study to a number of protein variants, arising from alternative mRNA splicing, of each of the three eIF4E isoforms. Our results surprisingly uncovered differences in the ability of eIF4E1_1 and eIF4E1_3 to form stress granules in response to cellular stresses.
CONCLUSION
Our comparison of all three human eIF4E isoforms and their protein variants enriches the intriguing spectrum of roles attributed to the eukaryotic initiation translation factors of the 4E family, which exhibit a distinctive localization within different RNA granules under different stresses. The localization of eIF4E3_A to stress granules, but not to processing bodies, along with its binding to eIF4G and PABP1 suggests a role of human eIF4E3_A in translation initiation rather than its involvement in a translational repression and mRNA decay and turnover. The localization of eIF4E2 to stress granules under heat shock but not arsenite stress indicates its distinct function in cellular response to these stresses and points to the variable protein content of SGs as a consequence of different stress insults.
Topics: Amino Acid Sequence; Cell Line; Cloning, Molecular; Cytosol; Eukaryotic Initiation Factor-4E; HEK293 Cells; Heat-Shock Response; Humans; Oxidative Stress; Poly(A)-Binding Protein I; RNA Cap-Binding Proteins; RNA, Messenger; Sequence Alignment
PubMed: 27578149
DOI: 10.1186/s12867-016-0072-x -
Cells Jun 2022Cells possess membraneless ribonucleoprotein (RNP) granules, including stress granules, processing bodies, Cajal bodies, or paraspeckles, that play physiological or... (Review)
Review
Cells possess membraneless ribonucleoprotein (RNP) granules, including stress granules, processing bodies, Cajal bodies, or paraspeckles, that play physiological or pathological roles. RNP granules contain RNA and numerous RNA-binding proteins, transiently formed through the liquid-liquid phase separation. The assembly or disassembly of numerous RNP granules is strongly controlled to maintain their homeostasis and perform their cellular functions properly. Normal RNA granules are reversibly assembled, whereas abnormal RNP granules accumulate and associate with various neurodegenerative diseases. This review summarizes current studies on the physiological or pathological roles of post-translational modifications of various cellular RNP granules and discusses the therapeutic methods in curing diseases related to abnormal RNP granules by autophagy.
Topics: Cytoplasmic Granules; Cytoplasmic Ribonucleoprotein Granules; Protein Processing, Post-Translational; RNA-Binding Proteins; Ribonucleoproteins
PubMed: 35805146
DOI: 10.3390/cells11132063 -
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 -
Plant Physiology Jan 2018Discoveries illuminate highly regulated dynamics of mRNA translation, sequestration, and degradation within the cytoplasm of plants. (Review)
Review
Discoveries illuminate highly regulated dynamics of mRNA translation, sequestration, and degradation within the cytoplasm of plants.
Topics: Cytoplasm; Cytoplasmic Granules; Polyribosomes; RNA Stability; RNA, Messenger; Stress, Physiological
PubMed: 29158329
DOI: 10.1104/pp.17.01468 -
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