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The folding of newly synthesized proteins to the native state is a major challenge within the crowded cellular environment, as non-productive interactions can lead to misfolding, aggregation and degradation 1 . Cells cope with this challenge by coupling synthesis with polypeptide folding and by using molecular chaperones to safeguard folding cotranslationally 2 . However, although most of the cellular proteome forms oligomeric assemblies 3 , little is known about the final step of folding: the assembly of polypeptides into complexes. In prokaryotes, a proof-of-concept study showed that the assembly of heterodimeric luciferase is an organized cotranslational process that is facilitated by spatially confined translation of the subunits encoded on a polycistronic mRNA 4 . In eukaryotes, however, fundamental differences—such as the rarity of polycistronic mRNAs and different chaperone constellations—raise the question of whether assembly is also coordinated with translation. Here we provide a systematic and mechanistic analysis of the assembly of protein complexes in eukaryotes using ribosome profiling. We determined the in vivo interactions of the nascent subunits from twelve hetero-oligomeric protein complexes of Saccharomyces cerevisiae at near-residue resolution. We find nine complexes assemble cotranslationally; the three complexes that do not show cotranslational interactions are regulated by dedicated assembly chaperones 5 – 7 . Cotranslational assembly often occurs uni-directionally, with one fully synthesized subunit engaging its nascent partner subunit, thereby counteracting its propensity for aggregation. The onset of cotranslational subunit association coincides directly with the full exposure of the nascent interaction domain at the ribosomal tunnel exit. The action of the ribosome-associated Hsp70 chaperone Ssb 8 is coordinated with assembly. Ssb transiently engages partially synthesized interaction domains and then dissociates before the onset of partner subunit association, presumably to prevent premature assembly interactions. Our study shows that cotranslational subunit association is a prevalent mechanism for the assembly of hetero-oligomers in yeast and indicates that translation, folding and the assembly of protein complexes are integrated processes in eukaryotes. Cotranslational assembly is a prevalent mechanism for the formation of oligomeric complexes in Saccharomyces cerevisiae , with one subunit serving as scaffold for the translation of partner subunits.

This research study investigated the production and properties of zinc oxide (ZnO) nanoparticles derived from corn husks and their priming effects on wheat plant proliferation and antioxidant mechanisms compared to the nutri-priming technique under regular irrigation and drought-stressed conditions. Transmission and scanning electron microscopy (TEM and SEM), energy-dispersive X-ray spectroscopy (EDAX), and X-ray diffraction confirmed the nanoparticles’ hexagonal morphology and typical dimensions of 51 nm. The size and stability of these nanoparticles were assessed through the size distribution and zeta potential analysis, indicating reasonable stability. Fourier-transform infrared spectroscopy (FTIR) detected the newly formed functional groups. This study emphasized the role of reactive oxygen species (ROS) and phenolic compounds in plant responses to nanoparticle treatment, particularly in detoxifying harmful radicals. The research also examined the activity of antioxidant enzymes, including peroxidase (POX), catalase (CAT), and glutathione reductase (GR), in alleviating stress caused by oxidation while subjected to various treatments, including micronutrient seed priming with DR GREEN fertilizer. Some biochemical compounds, such as total phenolics (TPCs), total flavonoids (TFCs), and total hydrolysable sugars, were estimated as well to show the effect of the different treatments on the wheat plants. The findings suggested that ZnO nanoparticles can enhance antioxidant enzyme activity under certain conditions while posing phytotoxic risks, underscoring the complexity of plant–nanoparticle interactions and the potential for improving crop resilience through targeted micronutrient applications.

Salinity reduces crop yields and quality, causing global economic losses. Zinc oxide nanoparticles (ZnO-NPs) improve plant physiological and metabolic processes and abiotic stress resistance. This study examined the effects of foliar ZnO-NPs at 75 and 150 mg/L on tomato Kecskeméti 549 plants to alleviate salt stress caused by 150 mM NaCl. The precipitation procedure produced ZnO-NPs that were characterized using UV-VIS, TEM, STEM, DLS, EDAX, Zeta potential, and FTIR. The study assessed TPCs, TFCs, total hydrolyzable sugars, total free amino acids, protein, proline, H2O2, and MDA along with plant height, stem width, leaf area, and SPAD values. The polyphenolic burden was also measured by HPLC. With salt stress, plant growth and chlorophyll content decreased significantly. The growth and development of tomato plants changed by applying the ZnO-NPs. Dosages of ZnO-NPs had a significant effect across treatments. ZnO-NPs also increased chlorophyll, reduced stress markers, and released phenolic chemicals and proteins in the leaves of tomatoes. ZnO-NPs reduce salt stress by promoting the uptake of minerals. ZnO-NPs had beneficial effects on tomato plants when subjected to salt stress, making them an alternate technique to boost resilience in saline soils or low-quality irrigation water. This study examined how foliar application of chemically synthesized ZnO-NPs to the leaves affected biochemistry, morphology, and phenolic compound synthesis with and without NaCl.

Salinity reduces crop yields and quality, causing global economic losses. Zinc oxide nanoparticles (ZnO-NPs) improve plant physiological and metabolic processes and abiotic stress resistance. This study examined the effects of foliar ZnO-NPs at 75 and 150 mg/L on tomato Kecskeméti 549 plants to alleviate salt stress caused by 150 mM NaCl. The precipitation procedure produced ZnO-NPs that were characterized using UV-VIS, TEM, STEM, DLS, EDAX, Zeta potential, and FTIR. The study assessed TPCs, TFCs, total hydrolyzable sugars, total free amino acids, protein, proline, H[sub.2] O[sub.2] , and MDA along with plant height, stem width, leaf area, and SPAD values. The polyphenolic burden was also measured by HPLC. With salt stress, plant growth and chlorophyll content decreased significantly. The growth and development of tomato plants changed by applying the ZnO-NPs. Dosages of ZnO-NPs had a significant effect across treatments. ZnO-NPs also increased chlorophyll, reduced stress markers, and released phenolic chemicals and proteins in the leaves of tomatoes. ZnO-NPs reduce salt stress by promoting the uptake of minerals. ZnO-NPs had beneficial effects on tomato plants when subjected to salt stress, making them an alternate technique to boost resilience in saline soils or low-quality irrigation water. This study examined how foliar application of chemically synthesized ZnO-NPs to the leaves affected biochemistry, morphology, and phenolic compound synthesis with and without NaCl.

Type 2 diabetes mellitus (T2DM) is increasingly recognized as a condition influenced by gut microbiota composition and associated metabolic pathways. This study investigated the differences in gut microbial diversity, composition, and metabolomic profiles between diabetic and control individuals. Using 16 S rRNA gene sequencing and metabolomic analyses, we observed significantly higher microbial diversity and evenness in the diabetic group, with distinct clustering patterns as revealed by Principal Coordinate Analysis (PCoA). Taxonomic profiling demonstrated an increased relative abundance of Bacteroidaceae and Lachnospiraceae in the diabetic group, while Streptococcaceae was more prevalent in the control group. LEfSe analysis identified key microbial taxa such as Bacteroides , Blautia , and Lachnospiraceae_FCS020_group enriched in diabetic individuals, suggesting a role in metabolic dysregulation. Metabolomic pathway enrichment analysis revealed significant differences in pathways related to fatty acid metabolism, glucose homeostasis, bile acid metabolism, and amino acid biosynthesis in diabetic individuals. Enriching fatty acid elongation and β-oxidation pathways, alongside disrupted glucose metabolism, indicate profound metabolic changes associated with diabetes. Bile acid metabolism and branched-chain amino acid (BCAA) pathways were also elevated, linking these metabolites to the observed gut microbiota shifts. These findings suggest that diabetes is associated with significant alterations in the gut microbiome’s composition and function, leading to disruptions in critical metabolic pathways. This study provides insights into potential microbial biomarkers and therapeutic targets for improving metabolic health in diabetic patients.

When cells encounter environmental stress, they rapidly mount an adaptive response by switching from pro-growth to stress-responsive gene expression programs. It is poorly understood how cells selectively silence pre-existing, pro-growth transcripts, yet efficiently translate transcriptionally-induced stress mRNA, and whether these transcriptional and post-transcriptional responses are coordinated. Here, we show that following acute glucose withdrawal in S. cerevisiae, pre-existing mRNAs are not first degraded to halt protein synthesis, nor are they sequestered away in P-bodies. Rather, their translation is rapidly repressed through a sequence-independent mechanism that differentiates between mRNAs produced before and after stress followed by their decay. Transcriptional induction of endogenous transcripts and reporter mRNAs during stress is sufficient to escape translational repression, while induction prior to stress leads to repression. Our results reveal a timing-controlled coordination of the transcriptional and translational responses in the nucleus and cytoplasm ensuring a rapid and widescale reprogramming of gene expression following environmental stress.

Nuclear mRNA export via nuclear pore complexes is an essential step in eukaryotic gene expression. Although factors involved in mRNA transport have been characterized, a comprehensive mechanistic understanding of this process and its regulation is lacking. Here, we use single-RNA imaging in yeast to show that cells use mRNA retention to control mRNA export during stress. We demonstrate that upon glucose withdrawal the essential RNA-binding factor Nab2 forms RNA-dependent condensate-like structures in the nucleus. This coincides with a reduced abundance of the DEAD-box ATPase Dbp5 at the nuclear pore. Depleting Dbp5, and consequently blocking mRNA export, is necessary and sufficient to trigger Nab2 condensation. The state of Nab2 condensation influences the extent of nuclear mRNA accumulation and can be recapitulated in vitro, where Nab2 forms RNA-dependent liquid droplets. We hypothesize that cells use condensation to regulate mRNA export and to control gene expression during stress. The nuclear poly(A)-binding protein Nab2 forms RNA-containing condensate-like structures upon glucose starvation and upon acute cellular depletion of the DEAD-box ATPase Dbp5 The Nab2 multimerization interface but not the intrinsically disordered regions (IDRs) are essential for condensation in vitro and in vivo Glucose stress leads to poly(A) RNA retention in the nucleus, which is affected by the state of the Nab2 condensate

Unidirectional transport of mRNA from the nucleus to the cytoplasm via nuclear pore complexes is an essential step in the gene expression of all eukaryotes. Although factors involved in mRNA transport have been characterized, a comprehensive mechanistic understanding of this critical process and its regulation is lacking. Here, we use real-time single RNA imaging to demonstrate that acute depletion of the budding yeast DEAD-box ATPase Dbp5 causes rapid nuclear accumulation of mRNAs in vivo and dramatic changes in nuclear dynamics of RNA export factors. In particular, the essential export factor Nab2 ceases to shuttle between the nucleus and cytoplasm and forms an RNA-dependent condensate throughout the nucleus. Phase-separation can be recapitulated in vitro, with Nab2 forming RNA-dependent liquid droplets, which depend on the presence of Dbp5. Intriguingly, in glucose stress, condensation of Nab2 blocks bulk mRNA export while selectively allowing the passage of stress-induced mRNAs from the nucleus to the cytoplasm to elicit a timely cellular stress response. This is accompanied by a lowered abundance of the DEAD-box ATPase Dbp5 at the cytoplasmic sites of nuclear pore complexes, which leads to the formation of the Nab2 condensates. Our results suggest that cells use selective mRNA retention in nuclear Nab2 condensates to re-wire mRNA export and to regulate gene expression during stress. Competing Interest Statement The authors have declared no competing interest.

N-terminal (Nt)-acetylation is a highly prevalent co-translational protein modification in eukaryotes, catalyzed by at least five Nt-acetyltransferases (Nat) with differing specificities. Nt-acetylation has been implicated in protein quality control but its broad biological significance remains elusive. We investigated the roles of the two major Nats of S. cerevisiae, NatA and NatB, by performing transcriptome, translatome and proteome profiling of natAΔ and natBΔ mutants. Our results do not support a general role of Nt-acetylation in protein degradation but reveal an unexpected range of Nat-specific phenotypes. NatA is implicated in systemic adaptation control, as natAΔ mutants display altered expression of transposons, sub-telomeric genes, pheromone response genes and nuclear genes encoding mitochondrial ribosomal proteins. NatB predominantly affects protein folding, as natBΔ mutants accumulate protein aggregates, induce stress responses and display reduced fitness in absence of the ribosome-associated chaperone Ssb. These phenotypic differences indicate that controlling Nat activities may serve to elicit distinct cellular responses.

This study aimed to examine whether or not aluminum chloride (AlCl 3 )-induced hepatotoxicity might be mitigated using magnetic water (MW) in rats. This study involved 28 adult male rats randomly assigned into the following 4 groups (7 rats/group): normal control (Cnt), MW, AlCl 3 , and Al Cl 3  + MW. The Cnt group orally received normal saline, the MW group drank MW ad libitum for 2 months, and the AlCl 3 and AlCl 3  + MW groups were orally administered AlCl 3 (40 mg/kg b.w.) alone or in combination with MW for 2 months, respectively. MW reduced AlCl 3 toxicity as proved at functional, molecular, and structural levels. Functionally, MW reduced serum levels of liver enzymes (ALT, AST, ALP, GGT), while increased total proteins, and albumin. MW also restored redox balance in the liver (lower MDA levels, higher activities of CAT and SOD enzymes, and upregulated expression of NrF2 , HO-1 , and GST genes. Molecularly, MW downregulated hepatic expression of the epigenetic ( HDAC3 ), inflammatory ( IL1β , TNFα , NFκβ ), and endoplasmic reticulum stress ( XBP1 , BIP , CHOP ) genes. Structurally, MW enhanced liver histology. With these results, we could conclude that MW has the potential to ameliorate the hepatotoxic effects of AlCl 3 through targeting oxidative stress, inflammation, epigenesis, and endoplasmic reticulum stress.