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We examined the transcriptome/post-transcriptome for persistent gene expression changes after radiation exposure in a baboon model. Eighteen baboons were irradiated with a whole body equivalent dose of 2.5 or 5 Gy. Blood samples were taken before, 7, 28 and 75–106 days after radiation exposure. Stage I was a whole genome screening for mRNA combined with a qRT-PCR platform for detection of 667 miRNAs. Candidate mRNAs and miRNAs differentially up- or down-regulated in stage I were chosen for validation in stage II using the remaining samples. Only 12 of 32 candidate genes provided analyzable results with two mRNAs showing significant 3–5-fold differences in gene expression over the reference (p < 0.0001). From 667 candidate miRNAs, 290 miRNA were eligible for analysis with 21 miRNAs independently validated using qRT-PCR. These miRNAs showed persistent expression changes on each day and over days 7–106 days after exposure (n = 7). In particular miR-212 involved in radiosensitivity and immune modulation appeared persistently and 48–77-fold up-regulated over the entire time period. We are finally trying to put our results into a context of clinical implications and provide possible hints on underlying molecular mechanisms to be examined in future studies.

Environmental salinity is an important abiotic factor influencing normal physiological functions and productive performance in the sea cucumber Apostichopus japonicus. It is therefore important to understand how changes in salinity affect sea cucumbers in the face of global climate change. In this study, we investigated the responses to salinity stress in sea cucumbers using mRNA and miRNA sequencing. The regulatory network of mRNAs and miRNAs involved in salinity stress was examined, and the metabolic pathways enriched for differentially expressed miRNAs and target mRNAs were identified. The top 20 pathways were involved in carbohydrate metabolism, fatty acid metabolism, degradation, and elongation, amino acid metabolism, genetic information processing, metabolism of cofactors and vitamins, transport and catabolism, and environmental information processing. A total of 22 miRNAs showed differential expression during salinity acclimation. The predicted 134 target genes were enriched in functions consistent with the results of gene enrichment based on transcriptome analysis. These results suggested that sea cucumbers deal with salinity stress via changes in amino acid metabolism, ion channels, transporters, and aquaporins, under stimulation by environmental signals, and that this process requires energy from carbohydrate and fatty acid metabolism. Salinity challenge also induced miRNA expression. These results provide a valuable genomic resource that extends our understanding of the unique biological characteristics of this economically important species under conditions of salinity stress.

miRNA arm switching is a pivotal regulatory mechanism that allows organisms to fine-tune gene expression by selectively utilizing either the 5p or 3p strand of a miRNA duplex. This process, conserved across species, facilitates adaptive responses to developmental cues, environmental changes, and disease states. By dynamically altering strand selection, arm switching reshapes gene regulatory networks, contributing to phenotypic diversity and evolutionary innovation. Despite its growing recognition, the mechanisms driving arm switching—such as thermodynamic properties and enzyme-mediated processing—remain incompletely understood. This review synthesizes current findings, highlighting arm switching as a highly conserved mechanism with profound implications for the evolution of regulatory networks. We explore how this phenomenon expands miRNA functionality, drives phenotypic plasticity, and co-evolves with miRNA gene duplications to fuel the diversification of biological functions across taxa.

Temporally regulated microRNAs have been identified as master regulators of developmental timing in both animals and plants. In plants, vegetative development is regulated by a temporal decrease in miR156 level, but how this decreased expression is initiated and then maintained during shoot development remains elusive. Here, we show that miR159 is required for the correct timing of vegetative development in Arabidopsis thaliana. Loss of miR159 increases miR156 level throughout shoot development and delays vegetative development, whereas overexpression of miR159 slightly accelerated vegetative development. The repression of miR156 by miR159 is predominantly mediated by MYB33, an R2R3 MYB domain transcription factor targeted by miR159. Loss of MYB33 led to subtle precocious vegetative phase change phenotypes in spite of the significant downregulation of miR156. MYB33 simultaneously promotes the transcription of MIR156A and MIR156C, as well as their target, SPL9, by directly binding to the promoters of these three genes. Rather than acting as major players in vegetative phase change in Arabidopsis, our results suggest that miR159 and MYB33 function as modifiers of vegetative phase change; i.e., miR159 facilitates vegetative phase change by repressing MYB33 expression, thus preventing MYB33 from hyperactivating miR156 expression throughout shoot development to ensure correct timing of the juvenile-to-adult transition in Arabidopsis.

Though clinical trials for medical applications of dimethyl sulfoxide (DMSO) reported toxicity in the 1960s, later, the FDA classified DMSO in the safest solvent category. DMSO became widely used in many biomedical fields and biological effects were overlooked. Meanwhile, biomedical science has evolved towards sensitive high-throughput techniques and new research areas, including epigenomics and microRNAs. Considering its wide use, especially for cryopreservation and in vitro assays, we evaluated biological effect of DMSO using these technological innovations. We exposed 3D cardiac and hepatic microtissues to medium with or without 0.1% DMSO and analyzed the transcriptome, proteome and DNA methylation profiles. In both tissue types, transcriptome analysis detected >2000 differentially expressed genes affecting similar biological processes, thereby indicating consistent cross-organ actions of DMSO. Furthermore, microRNA analysis revealed large-scale deregulations of cardiac microRNAs and smaller, though still massive, effects in hepatic microtissues. Genome-wide methylation patterns also revealed tissue-specificity. While hepatic microtissues demonstrated non-significant changes, findings from cardiac microtissues suggested disruption of DNA methylation mechanisms leading to genome-wide changes. The extreme changes in microRNAs and alterations in the epigenetic landscape indicate that DMSO is not inert. Its use should be reconsidered, especially for cryopreservation of embryos and oocytes, since it may impact embryonic development.

Cancer and other cells residing in the same niche engage various modes of interactions to synchronize and buffer the negative effects of environmental changes. Extracellular microRNAs (miRNAs) have recently been implicated in the intercellular crosstalk. Here we show a mechanistic model involving breast-cancer-secreted, extracellular-vesicle-encapsulated miR-105, which is induced by the oncoprotein MYC in cancer cells and, in turn, activates MYC signalling in cancer-associated fibroblasts (CAFs) to induce a metabolic program. This results in the capacity of CAFs to display different metabolic features in response to changes in the metabolic environment. When nutrients are sufficient, miR-105-reprogrammed CAFs enhance glucose and glutamine metabolism to fuel adjacent cancer cells. When nutrient levels are low and metabolic by-products accumulate, these CAFs detoxify metabolic wastes, including lactic acid and ammonium, by converting them into energy-rich metabolites. Thus, the miR-105-mediated metabolic reprogramming of stromal cells contributes to sustained tumour growth by conditioning the shared metabolic environment. Consistent crosstalk between cancer cells and stromal cells exists in the tumour microenvironment. Yan et al. show that exosomal miR-105 derived from cancer cells confers metabolic plasticity in recipient cancer-associated fibroblasts to adapt to nutrient-replete and -deplete conditions, thereby sustaining tumour growth.

Background Sooty mold (SM) disease severely threatens tea plant health, reducing yield and quality. Driven by climate change and intensive farming practices, SM prevalence in China has surged, causing significant economic losses and forcing farmers to rely on chemical fungicides, which compromise environmental sustainability. Despite its impact, the molecular mechanisms underlying tea plant defenses against SM remain unclear. Results Integrated transcriptomic, sRNAome, and degradome analyses revealed that differentially expressed genes (DEGs) exhibited infection-level-dependent expression patterns. Post-transcriptional regulation by miRNAs was identified through sRNAome-degradome mapping, with six miRNA-target defense pairs validated by 5′ RLM-RACE and qRT-PCR. Co-expression network analysis showed that two miRNA-target pairs, PC-5p-33681_128-auxin response factor ( CsARF ) and ppe-MIR535b-p3-1ss12TC-aldehyde dehydrogenase ( CsALDH ), play crucial roles in responding to SM infection. Furthermore, 5′ RLM-RACE and dual-luciferase assays revealed that the PC-5p-33681_128 and ppe-MIR535b-p3-1ss12TC could regulate the expression of CsARF and CsALDH by mRNA cleavage, respectively. Conclusion This study elucidates miRNA-mediated defense networks in tea plants against SM, offering actionable targets for breeding SM-resistant cultivars via genetic engineering or marker-assisted selection. Implementing these strategies could reduce yield losses, stabilize farmer incomes, and minimize environmental harm from fungicide overuse. This work advances climate-resilient practices for the global tea industry by linking molecular insights to sustainable agriculture.

Microglia-associated inflammation and miRNA dysregulation are key players in Alzheimer’s disease (AD) pathophysiology. Previously, we showed miR-124 upregulation in APP Swedish SH-SY5Y (SWE) and PSEN1 iPSC-derived neurons and its propagation by the secretome (soluble and exosomal fractions). After modulation with miR-124 mimic/inhibitor, we identified common responsive mechanisms between such models. We also reported miR-124 colocalization with microglia in AD patient hippocampi. Herein, we determined how miR-124 modulation in SWE cells influences microglia polarized subtypes in the context of inflammation. We used a coculture system without cell-to-cell contact formed by miR-124 modulated SWE cells and human CHME3 microglia stimulated with interferon-gamma (IFNγ-MG), in which we assessed their adopted gene/miRNA profile and proteomic signature. The increase of miR-124 in SWE cells/secretome (soluble and exosomal) was mimicked in IFNγ-MG. Treatment of SWE cells with the miR-124 inhibitor led to RAGE overexpression and loss of neuronal viability, while the mimic caused RAGE/HMGB1 downregulation and prevented mitochondria membrane potential loss. When accessing the paracrine effects on microglia, SWE miR-124 inhibitor favored their IFNγ-induced inflammatory signature (upregulated RAGE/HMGB1/iNOS/IL-1β; downregulated IL-10/ARG-1), while the mimic reduced microglia activation (downregulated TNF-α/iNOS) and deactivated extracellular MMP-2/MMP-9 levels. Microglia proteomics identified 113 responsive proteins to SWE miR-124 levels, including a subgroup of 17 proteins involved in immune function/inflammation and/or miR-124 targets. A total of 72 proteins were downregulated (e.g., MAP2K6) and 21 upregulated (e.g., PAWR) by the mimic, while the inhibitor also upregulated 21 proteins and downregulated 17 (e.g., TGFB1, PAWR, and EFEMP1). Other targets were associated with neurodevelopmental mechanisms, synaptic function, and vesicular trafficking. To examine the source of miR-124 variations in microglia, we silenced the RNase III endonuclease Dicer1 to block miRNA canonical biogenesis. Despite this suppression, the coculture with SWE cells/exosomes still raised microglial miR-124 levels, evidencing miR-124 transfer from neurons to microglia. This study is pioneer in elucidating that neuronal miR-124 reshapes microglia plasticity and in revealing the relevance of neuronal survival in mechanisms underlying inflammation in AD-associated neurodegeneration. These novel insights pave the way for the application of miRNA-based neuropharmacological strategies in AD whenever miRNA dysregulated levels are identified during patient stratification.

Although microRNAs are being extensively studied for their involvement in cancer and development, little is known about their roles in Alzheimer's disease (AD). In this study, we used microarrays for the first joint profiling and analysis of miRNAs and mRNAs expression in brain cortex from AD and age-matched control subjects. These data provided the unique opportunity to study the relationship between miRNA and mRNA expression in normal and AD brains. Using a non-parametric analysis, we showed that the levels of many miRNAs can be either positively or negatively correlated with those of their target mRNAs. Comparative analysis with independent cancer datasets showed that such miRNA-mRNA expression correlations are not static, but rather context-dependent. Subsequently, we identified a large set of miRNA-mRNA associations that are changed in AD versus control, highlighting AD-specific changes in the miRNA regulatory system. Our results demonstrate a robust relationship between the levels of miRNAs and those of their targets in the brain. This has implications in the study of the molecular pathology of AD, as well as miRNA biology in general.

Heat stress is one of the significant constraints affecting wheat production worldwide. To ensure food security for ever-increasing world population, improving wheat for heat stress tolerance is needed in the presently drifting climatic conditions. At the molecular level, heat stress tolerance in wheat is governed by a complex interplay of various heat stress-associated genes. We used a comparative transcriptome sequencing approach to study the effect of heat stress (5°C above ambient threshold temperature of 20°C) during grain filling stages in wheat genotype K7903 (Halna). At 7 DPA (days post-anthesis), heat stress treatment was given at four stages: 0, 24, 48, and 120 h. In total, 115,656 wheat genes were identified, including 309 differentially expressed genes (DEGs) involved in many critical processes, such as signal transduction, starch synthetic pathway, antioxidant pathway, and heat stress-responsive conserved and uncharacterized putative genes that play an essential role in maintaining the grain filling rate at the high temperature. A total of 98,412 Simple Sequences Repeats (SSR) were identified from de novo transcriptome assembly of wheat and validated. The miRNA target prediction from differential expressed genes was performed by psRNATarget server against 119 mature miRNA. Further, 107,107 variants including 80,936 Single nucleotide polymorphism (SNPs) and 26,171 insertion/deletion (Indels) were also identified in de novo transcriptome assembly of wheat and wheat genome Ensembl version 31. The present study enriches our understanding of known heat response mechanisms during the grain filling stage supported by discovery of novel transcripts, microsatellite markers, putative miRNA targets, and genetic variant. This enhances gene functions and regulators, paving the way for improved heat tolerance in wheat varieties, making them more suitable for production in the current climate change scenario.