Translational Repression Research Articles

Exploring the dynamics of messenger ribonucleoprotein-mediated translation repression.

Translational control is crucial for well-balanced cellular function and viability of organisms. Different mechanisms have evolved to up- and down-regulate protein synthesis, including 3' untranslated region (UTR)-mediated translation repression. RNA binding proteins or microRNAs interact with regulatory sequence elements located in the 3' UTR and interfere most often with the rate-limiting initiation step of translation. Dysregulation of post-transcriptional gene expression leads to various kinds of diseases, emphasizing the significance of understanding the mechanisms of these processes. So far, only limited mechanistic details about kinetics and dynamics of translation regulation are understood. This mini-review focuses on 3' UTR-mediated translational regulation mechanisms and demonstrates the potential of using single-molecule fluorescence-microscopy for kinetic and dynamic studies of translation regulation in vivo and in vitro.

The 4EHP-mediated translational repression of cGAS impedes the host immune response against DNA viruses

A critical host response against viral infections entails the activation of innate immune signaling that culminates in the production of antiviral proteins. DNA viruses are sensed by the cytosolic pattern recognition receptor cyclic GMP-AMP synthase (cGAS), which initiates a signaling pathway that results in production of proinflammatory cytokines such as Interferon-β (IFN-β) and activation of the antiviral response. Precise regulation of the antiviral innate immune response is required to avoid deleterious effects of its overactivation. We previously reported that the 4EHP/GIGYF2 translational repressor complex reduces the translation of Ifnb1 mRNA, which encodes IFN-β, upon RNA viral infections. Here, we report a distinct regulatory mechanism by which 4EHP controls replication of DNA viruses by translational repression of the Cgas mRNA, which encodes the DNA viral sensor cGAS. We show that 4EHP is required for effective translational repression of Cgas mRNA triggered by miR-23a. Upon infection, 4EHP deficiency bolsters the elicited innate immune response against the diverse DNA viruses Herpes simplex virus 1 (HSV-1) and Vaccinia Virus (VacV) and concomitantly reduces their rate of replication in vitro and in vivo. This study elucidates an intrinsic regulatory mechanism of the host response to DNA viruses which may provide unique opportunities for countering viral infections.

Identification of a New Role of miR-199a-5p as Factor Implied in Neuronal Damage: Decreasing the Expression of Its Target X-Linked Anti-Apoptotic Protein (XIAP) After SCI.

Spinal cord injury (SCI) results in a cascade of primary and secondary damage, with apoptosis being a prominent cause of neuronal cell death. The X-linked inhibitor of apoptosis (XIAP) plays a critical role in inhibiting apoptosis, but its expression is reduced following SCI, contributing to increased neuronal vulnerability. This study investigates the regulatory role of miR-199a-5p on XIAP expression in the context of SCI. Using bioinformatic tools, luciferase reporter assays, and in vitro and in vivo models of SCI, we identified miR-199a-5p as a post-transcriptional regulator of XIAP. Overexpression of miR-199a-5p significantly reduced XIAP protein levels, although no changes were observed at the mRNA level, suggesting translational repression. In vivo, miR-199a-5p expression was upregulated at 3 and 7 days post-injury, while XIAP expression inversely decreased in both neurons and oligodendrocytes, being particularly significant in the latter at 7 dpi. These findings suggest that miR-199a-5p contributes to the downregulation of XIAP and may exacerbate neuronal apoptosis after SCI. Targeting miR-199a-5p could offer a potential therapeutic strategy to modulate XIAP levels and reduce apoptotic cell death in SCI.

Investigating Ligand-Mediated Conformational Dynamics of Pre-miR21: A Machine-Learning-Aided Enhanced Sampling Study.

MicroRNAs (miRs) are short, noncoding RNA strands that regulate the activity of mRNAs by affecting the repression of protein translation, and their dysregulation has been implicated in several pathologies. miR21 in particular has been implicated in tumorigenesis and anticancer drug resistance, making it a critical target for drug design. miR21 biogenesis involves precise biochemical pathways, including the cleavage of its precursor, pre-miR21, by the enzyme Dicer. The present work investigates the conformational dynamics of pre-miR21, focusing on the role of adenine29 in switching between Dicer-binding-prone and inactive states. We also investigated the effect of L50, a cyclic peptide binder of pre-miR21 and a weak inhibitor of its processing. Using time series data and our novel collective variable-based enhanced sampling technique, OneOPES, we simulated these conformational changes and assessed the effect of L50 on the conformational plasticity of pre-miR21. Our results provide insight into peptide-induced conformational changes and pave the way for the development of a computational platform for the screening of inhibitors of pre-miR21 processing that considers RNA flexibility, a stepping stone for effective structure-based drug design, with potentially broad applications in drug discovery.

Serum microRNA Biomarker Expression in HIV and TB: A Concise Overview.

Non-coding RNAs (ncRNAs), specifically MicroRNAs or miRNAs, are now under-stood to be essential regulators in the complex field of gene expression. By selectively bind-ing to certain mRNA targets, these tiny RNA molecules control the expression of genes., leading to mRNA degradation or translational repression. The discovery of miRNAs has sig-nificantly advanced biomedical research, particularly in elucidating the molecular mecha-nisms underlying various diseases and exploring innovative therapeutic approaches. Recent progress in miRNA research has provided insights into their biogenesis, functional roles, and potential clinical applications. Despite the absence of established methodologies for clinical implementation, miRNAs show great promise as diagnostic and therapeutic agents for a wide array of diseases. Their distinctive attributes, such as high specificity, sensitivity, and accessibility, position them as ideal candidates for biomarker development and targeted therapy. Achieving a comprehensive understanding of miRNA biology and functionality is crucial to fully harnessing their potential in medicine. Ongoing research efforts aim to un-ravel the intricate mechanisms of miRNA-mediated gene regulation and to develop novel approaches for utilizing miRNAs in disease diagnosis, prognosis, and treatment. This review provides a comprehensive analysis of current knowledge on miRNAs, focusing on their bio-genesis, regulatory mechanisms, and potential clinical applications. By synthesizing existing evidence and highlighting key research findings, this review aims to inspire further explora-tion into the diverse roles of miRNAs in health and disease. Ultimately, this endeavour could result in the development of innovative miRNA-based diagnostic and therapeutic strategies.

Investigating the role of RNA-binding protein Ssd1 in aneuploidy tolerance through network analysis.

RNA-binding proteins (RBPs) play critical cellular roles by mediating various stages of RNA life cycles. Ssd1, an RBP with pleiotropic effects, has been implicated in aneuploidy tolerance in Saccharomyces cerevisiae but its mechanistic role remains unclear. Here we used a network-based approach to inform on Ssd1's role in aneuploidy tolerance, by identifying and experimentally perturbing a network of RBPs that share mRNA targets with Ssd1. We identified RBPs whose bound mRNA targets significantly overlap with Ssd1 targets. For 14 identified RBPs, we then used a genetic approach to generate all combinations of genotypes for euploid and aneuploid yeast with an extra copy of chromosome XII, with and without SSD1 and/or the RBP of interest. Deletion of 10 RBPs either exacerbated or alleviated the sensitivity of wild-type and/or ssd1∆ cells to chromosome XII duplication, in several cases indicating genetic interactions with SSD1 in the context of aneuploidy. We integrated these findings with results from a global over-expression screen that identified genes whose duplication complements ssd1∆ aneuploid sensitivity. The resulting network points to a sub-group of proteins with shared roles in translational repression and p-body formation, implicating these functions in aneuploidy tolerance. Our results reveal a role for new RBPs in aneuploidy tolerance and support a model in which Ssd1 mitigates translation-related stresses in aneuploid cells.

Cba-miR-222-3p involved in photoperiod-induced apoptosis in testes of striped hamsters by targeting TRAF7.

The role of miRNAs in the regulation of seasonal reproduction in rodents, particularly in relation to photoperiod changes, is still poorly understood. Previous studies on miRNA transcriptomes of striped hamster (Cricetulus barabensis) testes have indicated that the photoperiodism of testes, especially apoptosis, may be influenced by miRNAs. As a functional miRNA, cba-miR-222-3p in striped hamster testes exhibits suppression under a short photoperiod. To elucidate the potential role of testicular cba-miR-222-3p in the seasonal reproduction of striped hamsters, we exposed male striped hamsters to different photoperiods or injected miRNA agomir into the testes and observed the effects of these treatments, particularly some indicators related to apoptosis. The results showed that the levels of apoptosis in the testes increased in short daylength, accompanied by a significant decrease in cba-miR-222-3p expression and an increase in TRAF7 expression. Dual luciferase reporter assays verified the targeting relationship between cba-miR-222-3p and TRAF7 predicted by bioinformatics. In addition, the expression of TRAF7 decreased in the testes, which injected miRNA agomir, leading to inhibition of apoptosis, and the expression of key genes (MEKK3, p38, p53) in the downstream MAPK signaling pathway of TRAF7 was suppressed. These results suggest that short daylength induces testicular apoptosis in striped hamsters, and one possible mechanism is that the decreased expression of miR-222-3p in testes reduces the repression of TRAF7 translation, thereby activating the MAPK pathway and affecting the level of testicular apoptosis. These findings reveal the potential role of miR-222-3p in animal reproduction and provide new insights into the regulation of rodent populations.

A conserved fungal morphogenetic kinase regulates pathogenic growth in response to carbon source diversity

Fungal pathogens must exhibit strong nutritional plasticity, effectively sensing and utilizing diverse nutrients to support virulence. How the signals generated by nutritional sensing are efficiently translated to the morphogenetic machinery for optimal growth and support of virulence remains incompletely understood. Here, we show that the conserved morphogenesis-related kinase, CotA, imparts isoform-specific control over Aspergillus fumigatus invasive growth in host-mimicking environments and during infection. CotA-mediated invasive growth is responsive to exogenous carbon source quality, with only preferred carbon sources supporting hyphal morphogenesis in a mutant lacking one of two identified protein isoforms. Strikingly, we find that the CotA protein does not regulate, nor is cotA gene expression regulated by, the carbon catabolite repression system. Instead, we show that CotA partially mediates invasive growth in specific carbon sources and virulence through the conserved downstream effector and translational repressor, SsdA. Therefore, A. fumigatus CotA accomplishes its conserved morphogenetic functions to drive pathogenic growth by translating host-relevant carbon source quality signals into morphogenetic outputs for efficient tissue invasive growth.

Prefrontal TNRC6A mediates anxiety-like behaviour by regulating CRF through the maintenance of miR-21-3p stability

Anxiety is an emotional response to a potential threat. It is characterized by worry, feelings of tension, and physical changes. Trinucleotide repeat containing adaptor 6A (TNRC6A) binds to argonaute (AGO) proteins and microRNAs to form the miRNA-induced silencing complex (miRISC), which mediates mRNA degradation, storage, and translational repression functions. However, whether TNRC6A is involved in anxiety regulation remains unknown.In this study, TNRC6A was downregulated in the prefrontal cortex (PFC) of mice exposed to acute restraint stress. Inhibition of TNRC6A in PFC induced anxious behaviour. RNA immunoprecipitation, RNA pull-down and real-time quantitative PCR revealed that TNRC6A directly binds to miR-21-3p and maintains its stability. Intriguingly, miR-21-3p was downregulated in the PFC of acute stress mice, whereas overexpression of miR-21-3p significantly reduced anxiety-like behaviour. Furthermore, miR-21-3p knockdown significantly increased the frequency and amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) in the PFC pyramidal neurons. Dual luciferase assay and western blotting confirmed that miR-21-3p binds to the 3 ‘UTR region of corticotropin-releasing factor (CRF) mRNA and regulates CRF and cAMP-response element binding protein (CREB) expression. These results confirm that low levels of TNRC6A in the PFC decrease the stability of miR-21-3p which promotes the up-regulation of CRF, leading to the development of anxiety-like behaviours. This research provides insight into a novel molecular mechanism by which TNRC6A regulates anxiety behaviour through the miR-21-3p/CRF signalling axis.

Widespread regulation of the maternal transcriptome by Nanos in Drosophila.

The translational repressor Nanos (Nos) regulates a single target, maternal hunchback (hb) mRNA, to govern abdominal segmentation in the early Drosophila embryo. Nos is recruited to sites in the 3' UTR of hb mRNA in collaboration with the sequence-specific RNA-binding protein Pumilio (Pum); on its own, Nos has no binding specificity. Nos is expressed at other stages of development, but very few mRNA targets that might mediate its action at these stages have been described. Nor has it been clear whether Nos is targeted to other mRNAs in concert with Pum or via other mechanisms. In this report, we identify mRNAs targeted by Nos via 2 approaches. First, we identify mRNAs depleted upon expression of a chimera bearing Nos fused to the nonsense mediated decay (NMD) factor Upf1. We find that, in addition to hb, Upf1-Nos depletes approximately 2,600 mRNAs from the maternal transcriptome in early embryos. Virtually all of these appear to be targeted in a canonical, hb-like manner in concert with Pum. In a second, more conventional approach, we identify mRNAs that are stabilized during the maternal zygotic transition (MZT) in embryos from nos- females. Most (86%) of the 1,185 mRNAs regulated by Nos are also targeted by Upf1-Nos, validating use of the chimera. Previous work has shown that 60% of the maternal transcriptome is degraded in early embryos. We find that maternal mRNAs targeted by Upf1-Nos are hypoadenylated and inefficiently translated at the ovary-embryo transition; they are subsequently degraded in the early embryo, accounting for 59% of all destabilized maternal mRNAs. We suggest that the late ovarian burst of Nos represses a large fraction of the maternal transcriptome, priming it for later degradation by other factors in the embryo.

MicroRNAs as Indicators of Alterations in Reaction to Endurance Training

Without a doubt, endurance sports are beneficial for heart health and general fitness; regular physical exercise is thought to be one of the best ways to avoid cardiovascular disease. Gene expression is regulated by tiny molecules known as microRNAs, which are generated subsequent to transcription. Translational repression, mRNA deadenylation, and decapping are all caused by miRNAs when they attach to a certain region at the 3′ UTR of their target mRNAs (40, 41). Along with promoter regions, additional mRNA regions such as the 5′ UTR and coding sequence have also been shown to include miRNA binding sites. While it has been shown that miRNA contact with a promoter region may drive transcription, miRNA binding to the 5′ UTR and coding sections silences the expression of genes. According to preliminary research, miRNAs may serve as helpful indicators of the systemic changes brought on by exercise before they are identified using traditional imaging or laboratory methods. This study focused on four important physiological processes that help the body adapt to various endurance workouts. We found that miR-27, miR-221, miR-210, miR-328, miR-133a, miR-134a, and miR-20a are essential for adaptive response to exercise after conducting a thorough literature search.

MicroRNA miR-210 Modulates the Water Flea Daphnia magna Response to Cyanobacterial Toxicity.

As a key form of post-transcriptional regulation, microRNAs (miRNAs) regulate gene expression by binding to target mRNAs, leading to mRNA decay or translational repression. Recently, the role of miRNAs in the response of aquatic organisms to environmental stressors has emerged. Daphnia, widely distributed cladocerans, play a crucial role in aquatic ecosystems. Cyanobacterial blooms often cause Daphnia populations to decrease, thereby disrupting ecosystem functionality and water quality. However, the post-transcriptional mechanisms behind Daphnia's response to toxic cyanobacteria are insufficiently understood. This study investigated the role of miR-210, a multifunctional miRNA involved in stress response and toxicity pathways, and its target genes (MLH3, CDHR5, and HYOU1) in two Daphnia magna clones exposed to toxic Microcystis aeruginosa. Results showed that M. aeruginosa inhibited somatic growth rates, led to microcystin accumulation, caused abnormal ultrastructural alterations in the digestive tract, and induced DNA damage in both clones. Notably, exposure significantly increased miR-210 expression and decreased the expression of its target genes compared with the controls. We identified miR-210s regulation on clonal-tolerance variations in D. magna to M. aeruginosa, emphasizing miRNAs' contribution to adaptive responses. Our work uncovered a novel post-transcriptional mechanism of cyanobacterial impact on zooplankton and provided essential insights for assessing cyanobacterial toxicity risks.

BRCA1 levels and DNA-damage response are controlled by the competitive binding of circHIPK3 or FMRP to the BRCA1 mRNA

Circular RNAs (circRNAs) are covalently closed RNA molecules widely expressed in eukaryotes and deregulated in several pathologies, including cancer. Many studies point to their activity as microRNAs (miRNAs) and protein sponges; however, we propose a function based on circRNA-mRNA interaction to regulate mRNA fate. We show that the widely tumor-associated circHIPK3 directly interacts invivo with the BRCA1 mRNA through the back-splicing region in human cancer cells. This interaction increases BRCA1 translation by competing for the binding of the fragile-X mental retardation 1 protein (FMRP) protein, which we identified as a BRCA1 translational repressor. CircHIPK3 depletion or disruption of the circRNA-mRNA interaction decreases BRCA1 protein levels and increases DNA damage, sensitizing several cancer cells to DNA-damage-inducing agents and rendering them susceptible to synthetic lethality. Additionally, blocking FMRP interaction with BRCA1 mRNA with locked nucleic acid (LNA) restores physiological protein levels in BRCA1 hemizygous breast cancer cells, underscoring the importance of this circRNA-mRNA interaction in regulating DNA-damage response.

9343 Protection Against Type 1 Diabetes Development In Mice With 4E-BP2 Deletion

Abstract Disclosure: V. Pita Grisanti: None. F. Pecanha: None. R. Louzada: None. M. Blandino: None. C. Jaramillo: None. N. Arenas: None. A. Bayer: None. E. Bernal-Mizrachi: None. Type 1 diabetes is an autoimmune disease characterized by β-cell destruction promoted by autoreactive T cells that acquire an effector inflammatory phenotype. 4E-BP1/2 proteins are translational repressors and downstream targets of mTORC1, a key regulator of metabolism. mTORC1 signaling disruption is implicated in human diseases including diabetes. Activation of 4E-BP2/eIF4E pathway by 4E-BP2 deletion promotes translation initiation, which induces β-cell expansion and proliferation and is crucial for the regulation of adaptive immunity. However, the involvement of 4E-BP2 in type 1 diabetes development has not been explored. Therefore, this study aimed to determine the role of 4E-BP2/eIF4E signaling in type 1 diabetes prevention by regulation of β-cell survival and immune modulation. To investigate the role of 4E-BP2/eIF4E axis in diabetes pathogenesis, we used the non-obese diabetic (NOD) mouse model as a type 1 diabetes model, and generated mice with global deletion of 4E-BP2 in the NOD background (4E-BP2KONOD). We assessed type 1 diabetes development, glucose homeostasis, pancreas morphometry and immune responses in male and female 4E-BP2KONOD and control NOD mice. We found that 4E-BP2KONOD exhibited reduced diabetes incidence in male but not female mice. Reduction in diabetes incidence in 4E-BP2KONOD male mice was associated with comparable degree of insulitis and β-cell proliferation, and with preserved β-cell mass compared to the control NOD mice. Glucose-stimulated insulin secretion of the islets, assessed in vitro by static incubation, was significantly higher in the 4E-BP2KONOD compared to the NOD control. Autoimmune responses were also evaluated by assessment of insulitis and characterization of T cell compartments, which showed a decrease in splenic CD8+ cytotoxic T cells and an increase in pancreatic regulatory T cell (Treg) infiltration mainly by increased Treg survival in 4E-BP2KONOD mice compared to control NOD. Finally, adoptive transfer studies demonstrated that lymphocytes derived from male 4E-BP2KONOD mice were less diabetogenic than those derived from control NOD mice. In conclusion, this study showed that activation of 4E-BP2/eIF4E axis in 4E-BP2KONOD male mice protects against type 1 diabetes development by dampening autoimmune responses and preserving β-cell mass. Targeting 4E-BP2 may provide a potential treatment for type 1 diabetes. Presentation: 6/1/2024

Regulation of Bone Morphogenetic Protein Receptor Type II Expression by FMR1/Fragile X Mental Retardation Protein in Human Granulosa Cells in the Context of Poor Ovarian Response.

Fragile X mental retardation protein (FMRP) is a translational repressor encoded by FMR1. It targets bone morphogenetic protein receptor type II (BMPR2), which regulates granulosa cell (GC) function and follicle development. However, whether this interaction affects folliculogenesis remains unclear. Therefore, this study investigated the potential effect of FMRP-BMPR2 dysregulation in ovarian reserves and infertility. COV434 cells and patient-derived GCs were used to evaluate FMRP and BMPR2 expression. Similarly, FMR1, BMPR2, LIMK1, and SMAD expression were evaluated in GCs with normal (NOR) and poor (POR) ovarian responses. FMRP and BMPR2 were expressed in both cell types. They were co-localized to the nuclear membrane of COV434 cells and cytoplasm of primary GCs. FMR1 silencing increased the mRNA and protein levels of BMPR2. However, the mRNA levels of FMR1 and BMPR2 were significantly lower in the POR group. FMR1 and BMPR2 levels were strongly positively correlated in the NOR group but weakly correlated in the POR group. Additionally, SMAD9 expression was significantly reduced in the POR group. This study highlights the crucial role of FMR1/FMRP in the regulation of BMPR2 expression and its impact on ovarian function. These findings indicate that the disruption of FMRP-BMPR2 interactions may cause poor ovarian responses and infertility.

Regulatory, diagnostic, and therapeutic roles of microRNAs in chronic liver diseases.

Fibrogenesis is initially performed during tissue damage to protect the remaining tissues from the progressive death of epithelial cells, infiltration of immune and inflammatory cells, and local degrading enzymes. Inflammation can lead to excessive extracellular matrix deposition by fibroblasts and the induction of fibrosis in many organs, such as the liver. MiRNAs are small noncoding RNAs that mediate mRNA repression or destabilization, leading to translational repression. Owing to the wide range of roles of miRNAs in the development of fibrosis, especially liver fibrosis, many studies have focused on their diagnostic, regulatory, and therapeutic roles. In this study, we used medical science and general databases, including PubMed, Elsevier, Scopus, Nature, and Google Scholar, to find valid studies on the different roles of miRNAs in liver fibrosis. Because a large number of miRNAs with regulatory, diagnostic, and therapeutic roles in diseases associated with liver fibrosis have been identified and reported in this study, special attention to these elements is needed in the future of healthcare systems.

The CCT chaperonin and actin modulate the ER and RNA-binding protein condensation during oogenesis and maintain translational repression of maternal mRNA and oocyte quality.

The regulation of maternal mRNAs is essential for proper oogenesis, the production of viable gametes, and to avoid birth defects and infertility. Many oogenic RNA-binding proteins have been identified with roles in mRNA metabolism, some of which localize to dynamic ribonucleoprotein granules and others that appear dispersed. Here, we use a combination of in vitro condensation assays and the in vivo Caenorhabditis elegans oogenesis model to characterize the properties of the conserved KH-domain MEX-3 protein and to identify novel regulators of MEX-3 and three other translational regulators. We demonstrate that MEX-3 undergoes phase separation and appears to have intrinsic gel-like properties in vitro. We also identify novel roles for the chaperonin-containing tailless complex polypeptide 1 (CCT) chaperonin and actin in preventing ectopic RNA-binding protein condensates in maturing oocytes that appear to be independent of MEX-3 folding. The CCT chaperonin and actin also oppose the expansion of endoplasmic reticulum sheets that may promote ectopic condensation of RNA-binding proteins. These novel regulators of condensation are also required for the translational repression of maternal mRNA which is essential for oocyte quality and fertility. The identification of this regulatory network may also have implications for understanding the role of hMex3 phase transitions in cancer.

Discovery of a conserved translationally repressive upstream open reading frame within the iron-deficiency response regulator IDEF2

BackgroundIron (Fe) deficiency affects 30–50% of the world’s population. Genetic biofortification of staple crops is a promising strategy for improving human nutrition, but the number of effective precision breeding targets for Fe biofortification is small. Upstream open reading frames (uORFs) are cis-regulatory elements within the 5’ leader sequence (LS) of genes that generally repress translation of the main open reading frame (mORF).ResultsWe aligned publicly available rice (Oryza sativa L.) ribo-seq datasets and transcriptomes to identify putative uORFs within important Fe homeostasis genes. A dual luciferase assay (DLA) was used to determine whether these uORFs cause repression of mORF translation and pinpoint LS regions that can be mutated for mORF derepression. A translationally repressive uORF region was identified in two positive regulators of the Fe-deficiency response: IDEF1 and IDEF2. The IDEF2-uORF peptide was highly conserved among monocots and a mutation series in the 5’ LS of the wheat (Triticum aestivum L.) TaIDEF2-A1 gene demonstrated variable mORF derepression.ConclusionsTogether these results reveal a possible regulatory mechanism by which IDEF2 transcription factors modulate the Fe deficiency response in monocots, and highlight novel precision breeding targets to improve crop nutrition and abiotic stress tolerance.

Spatial organization of translation and translational repression in two phases of germ granules

Most RNA-protein condensates are composed of heterogeneous immiscible phases. However, how this multiphase organization contributes to their biological functions remains largely unexplored. Drosophila germ granules, a class of RNA-protein condensates, are the site of mRNA storage and translational activation. Here, using super-resolution microscopy and single-molecule imaging approaches, we show that germ granules have a biphasic organization and that translation occurs in the outer phase and at the surface of the granules. The localization, directionality, and compaction of mRNAs within the granule depend on their translation status, translated mRNAs being enriched in the outer phase with their 5′end oriented towards the surface. Translation is strongly reduced when germ granule biphasic organization is lost. These findings reveal the intimate links between the architecture of RNA-protein condensates and the organization of their different functions, highlighting the functional compartmentalization of these condensates.

Exploring the Role of the Processing Body in Plant Abiotic Stress Response.

The processing body (P-Body) is a membrane-less organelle with stress-resistant functions. Under stress conditions, cells preferentially translate mRNA that favors the stress response, resulting in a large number of transcripts unfavorable to the stress response in the cytoplasm. These non-translating mRNAs aggregate with specific proteins to form P-Bodies, where they are either stored or degraded. The protein composition of P-Bodies varies depending on cell type, developmental stage, and external environmental conditions. This review primarily elucidates the protein composition in plants and the assembly of P-Bodies, and focuses on the mechanisms by which various proteins within the P-Bodies of plants regulate mRNA decapping, degradation, translational repression, and storage at the post-transcriptional level in response to ethylene signaling and abiotic stresses such as drought, high salinity, or extreme temperatures. This overview provides insights into the role of the P-Body in plant abiotic stress responses.