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1. Regulatory links between the circadian clock and stress-induced biomolecular condensates

   https://doi.org/10.1038/s44323-025-00036-2  

   Brown, Gabriela; Nagel, Dawn H (December 2025, npj Biological Timing and Sleep)

   The circadian clock is a conserved timekeeping mechanism that is essential for integrating different environmental cues such as light and temperature to coordinate biological processes with the time of day. While much is known about transcriptional regulation by the clock, the role of post-transcriptional regulation, particularly through sequestration into biomolecular condensate such as stress granules, remains less understood. Stress granules are dynamic RNA-protein assemblies that play a critical role in the cellular response to stress by sequestering mRNAs to regulate translation during stressful conditions. In animals and fungi, the circadian clock regulates stress granule formation and mRNA translation by controlling key factors such as eIF2α, which orchestrates the rhythmic sequestration and translation of specific mRNAs. In plants, it has been shown that some transcripts, despite coming from arrhythmic expression, are rhythmically translated. In addition, some clock-controlled genes (CCGs) are induced in response to heat stress only at the transcriptional level and not at the translational level. Together this highlights a layer of clock regulation beyond transcription. This review discusses the intersection between the circadian clock and heat stress-related biomolecular condensates across eukaryotes, with a particular focus on plants. We discuss how the clock may regulate stress granule dynamics and preferential translation of mRNAs at specific times of the day or during stress responses, thereby enhancing cellular function and energy efficiency. By integrating evidence from animals, fungi, and plants, we highlight emerging questions regarding the role of biomolecular condensates as post-transcriptional mechanisms in controlling circadian rhythms and stress tolerance in plants. 

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2. RNA-Binding Proteins: The Key Modulator in Stress Granule Formation and Abiotic Stress Response

   https://doi.org/10.3389/fpls.2022.882596  

   Yan, Yanyan; Gan, Jianghuang; Tao, Yilin; Okita, Thomas W.; Tian, Li (June 2022, Frontiers in Plant Science)

   To cope with abiotic environmental stress, plants rapidly change their gene expression transcriptionally and post-transcriptionally, the latter by translational suppression of selected proteins and the assembly of cytoplasmic stress granules (SGs) that sequester mRNA transcripts. RNA-binding proteins (RBPs) are the major players in these post-transcriptional processes, which control RNA processing in the nucleus, their export from the nucleus, and overall RNA metabolism in the cytoplasm. Because of their diverse modular domain structures, various RBP types dynamically co-assemble with their targeted RNAs and interacting proteins to form SGs, a process that finely regulates stress-responsive gene expression. This review summarizes recent findings on the involvement of RBPs in adapting plants to various abiotic stresses via modulation of specific gene expression events and SG formation. The relationship of these processes with the stress hormone abscisic acid (ABA) is discussed. 

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3. Two eIF4E paralogs occupy separate germ granule messenger ribonucleoproteins that mediate mRNA repression and translational activation

   https://doi.org/10.1093/genetics/iyaf053  

   Gajjar, Gita; Huggins, Hayden P; Kim, Eun Suk; Huang, Weihua; Bonnet, Frederic X; Updike, Dustin L; Keiper, Brett D (March 2025, GENETICS)

   Kennedy, S (Ed.)

   Abstract We studied translation factor eukaryotic initiation factor 4E (eIF4E) paralogs that regulate germline mRNAs. Translational control of mRNAs is essential for germ cell differentiation and embryogenesis. Messenger ribonucleoprotein complexes assemble on mRNAs in the nucleus, as they exit via perinuclear germ granules, and in the cytoplasm. Bound messenger ribonucleoproteins including eIF4E exert both positive and negative posttranscriptional regulation. In Caenorhabditiselegans, germ granules are surprisingly dynamic messenger ribonucleoprotein condensates that remodel during development. Two eIF4E paralogs (IFE-1 and IFE-3), their cognate eIF4E–interacting proteins, and polyadenylated mRNAs are present in germ granules. Affinity purification of IFE-1 and IFE-3 messenger ribonucleoproteins allowed mass spectrometry and mRNA-Seq to identify other proteins and the mRNAs that populate stable eukaryotic initiation factor 4E complexes. We find translationally repressed mRNAs (e.g. pos-1, mex-3, spn-4, etc.) enriched with IFE-3, but excluded from IFE-1. Identified mRNAs overlap substantially with mRNAs previously described to be IFE-1 dependent for translation. The findings suggest that oocytes and embryos utilize the 2 eukaryotic initiation factor 4E paralogs for opposite purposes on critically regulated germline mRNAs. Sublocalization within adult perinuclear germ granules suggests an architecture in which Vasa/GLH-1, PGL-1, and the IFEs are stratified, which may facilitate sequential remodeling of messenger ribonucleoproteins leaving the nucleus. Biochemical composition of isolated messenger ribonucleoproteins indicates opposing yet cooperative roles for the 2 eukaryotic initiation factor 4E paralogs. We propose that the IFEs accompany controlled mRNAs in the repressed or activated state during transit to the cytoplasm. Copurification of IFE-1 with IFE-3 suggests they may interact to move repressed mRNAs to ribosomes. 

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4. Activation of Gαq sequesters specific transcripts into Ago2 particles

   https://doi.org/10.1038/s41598-022-12737-w  

   Jackson, Lela; Rennie, Madison; Poussaint, Alison; Scarlata, Suzanne (December 2022, Scientific Reports)

   Abstract The Gαq/phospholipase Cβ1 (PLCβ1) signaling system mediates calcium responses from hormones and neurotransmitters. While PLCβ1 functions on the plasma membrane, there is an atypical cytosolic population that binds Argonaute 2 (Ago2) and other proteins associated with stress granules preventing their aggregation. Activation of Gαq relocalizes cytosolic PLCβ1 to the membrane, releasing bound proteins, promoting the formation of stress granules. Here, we have characterized Ago2 stress granules associated with Gαq activation in differentiated PC12 cells, which have a robust Gαq/PLCβ1 signaling system. Characterization of Ago2-associated stress granules shows shifts in protein composition when cells are stimulated with a Gαq agonist, or subjected to heat shock or osmotic stress, consistent with the idea that different stresses result in unique stress granules. Purified Ago2 stress granules from control cells do not contain RNA, while those from heat shock contain many different mRNAs and miRs. Surprisingly, Ago2 particles from cells where Gαq was stimulated show only two transcripts, chromogranin B, which is involved in secretory function, and ATP synthase 5f1b, which is required for ATP synthesis. RT-PCR, western blotting and other studies support the idea that Gαq-activation protects these transcripts. Taken together, these studies show a novel pathway where Gαq/PLCβ regulates the translation of specific proteins. 

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5. Germ Granule Evolution Provides Mechanistic Insight into Drosophila Germline Development

   https://doi.org/10.1093/molbev/msad174  

   Doyle, Dominique A; Burian, Florencia N; Aharoni, Benjamin; Klinder, Annabelle J; Menzel, Melissa M; Nifras, Gerard Carlo; Shabazz-Henry, Ahad L; Palma, Bianca Ulrich; Hidalgo, Gisselle A; Sottolano, Christopher J; et al (August 2023, Molecular Biology and Evolution)

   True, John (Ed.)

   Abstract The copackaging of mRNAs into biomolecular condensates called germ granules is a conserved strategy to posttranscriptionally regulate germline mRNAs. In Drosophila melanogaster, mRNAs accumulate in germ granules by forming homotypic clusters, aggregates containing multiple transcripts from the same gene. Nucleated by Oskar (Osk), homotypic clusters are generated through a stochastic seeding and self-recruitment process that requires the 3′ untranslated region (UTR) of germ granule mRNAs. Interestingly, the 3′ UTR belonging to germ granule mRNAs, such as nanos (nos), have considerable sequence variations among Drosophila species and we hypothesized that this diversity influences homotypic clustering. To test our hypothesis, we investigated the homotypic clustering of nos and polar granule component (pgc) in four Drosophila species and concluded that clustering is a conserved process used to enrich germ granule mRNAs. However, we discovered germ granule phenotypes that included significant changes in the abundance of transcripts present in species’ homotypic clusters, which also reflected diversity in the number of coalesced primordial germ cells within their embryonic gonads. By integrating biological data with computational modeling, we found that multiple mechanisms underlie naturally occurring germ granule diversity, including changes in nos, pgc, osk levels and/or homotypic clustering efficacy. Furthermore, we demonstrated how the nos 3′ UTR from different species influences nos clustering, causing granules to have ∼70% less nos and increasing the presence of defective primordial germ cells. Our results highlight the impact that evolution has on germ granules, which should provide broader insight into processes that modify compositions and activities of other classes of biomolecular condensate. 

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