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1. Neuron enriched extracellular vesicles’ MicroRNA expression profiles as a marker of early life alcohol consumption

   https://doi.org/10.1038/s41398-024-02874-3  

   Yakovlev, Vasily; Lapato, Dana M; Rana, Pratip; Ghosh, Preetam; Frye, Rebekah; Roberson-Nay, Roxann (December 2024, Translational Psychiatry)

   Abstract Alcohol consumption may impact and shape brain development through perturbed biological pathways and impaired molecular functions. We investigated the relationship between alcohol consumption rates and neuron-enriched extracellular vesicles’ (EVs’) microRNA (miRNA) expression to better understand the impact of alcohol use on early life brain biology. Neuron-enriched EVs’ miRNA expression was measured from plasma samples collected from young people using a commercially available microarray platform while alcohol consumption was measured using the Alcohol Use Disorders Identification Test. Linear regression and network analyses were used to identify significantly differentially expressed miRNAs and to characterize the implicated biological pathways, respectively. Compared to alcohol naïve controls, young people reporting high alcohol consumption exhibited significantly higher expression of three neuron-enriched EVs’ miRNAs including miR-30a-5p, miR-194-5p, and miR-339-3p, although only miR-30a-5p and miR-194-5p survived multiple test correction. The miRNA-miRNA interaction network inferred by a network inference algorithm did not detect any differentially expressed miRNAs with a high cutoff on edge scores. However, when the cutoff of the algorithm was reduced, five miRNAs were identified as interacting with miR-194-5p and miR-30a-5p. These seven miRNAs were associated with 25 biological functions; miR-194-5p was the most highly connected node and was highly correlated with the other miRNAs in this cluster. Our observed association between neuron-enriched EVs’ miRNAs and alcohol consumption concurs with results from experimental animal models of alcohol use and suggests that high rates of alcohol consumption during the adolescent/young adult years may impact brain functioning and development by modulating miRNA expression. 

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2. Beta cell microRNAs function as molecular hubs of type 1 diabetes pathogenesis and as biomarkers of diabetes risk

   https://doi.org/10.1007/s00125-026-06720-7  

   Syed, Farooq; Krishnan, Preethi; Chang, Garrick; Rana, Jyoti; Langlais, Sarah R; Hati, Sumon; Yamada, Kentaro; Lam, Anh K; Talware, Sayali; Del_Carmen_Aquino, Jacqueline; et al (July 2026, Diabetologia)

   Clinically actionable biomarkers that accurately reflect the health status of the beta cell are needed to improve risk stratification and optimise the timing of interventions in type 1 diabetes. We hypothesised that inflammatory stress elicits a reproducible microRNA (miRNA) program in human islets and islet-derived extracellular vesicles (EVs) that can be detected in plasma EVs to stratify diabetes risk, while also providing insight into molecular pathways linked to beta cell dysfunction. MethodsHuman islets were exposed to IL-1β+IFN-γ, and small RNA-seq was performed on islets and islet-derived EVs. Differentially expressed miRNAs were validated in islets, using RT-PCR, in plasma-derived EVs from individuals with autoantibody positivity (AAb⁺) or recent-onset type 1 diabetes and matched control individuals using ultrasensitive, label-free localised surface plasmon resonance (LSPR) biosensors, and in pancreatic sections from organ donors using in situ hybridisation and spatial feature analysis. Finally, beta cell-targeted in vivo inhibition of miR-155 was tested in the NOD mouse model. ResultsInflammatory cytokine exposure altered a restricted subset of miRNAs, identifying 20 differentially expressed miRNAs in islets and 14 in islet-derived EVs. Only two miRNAs, miR-155-5p and miR-146a-5p, were concordantly upregulated in both compartments. Machine learning prioritised an EV miRNA panel for translational validation, and custom LSPR biosensors enabled quantification of these miRNAs in plasma EVs. This plasma EV miRNA signature, consisting of miR-155-5p, miR-146a-5p, miR-30c-1-3p, miR-802 and miR-124-3p, differentiated individuals with AAb⁺and those with recent-onset type 1 diabetes from control individuals with good sensitivity and specificity. In pancreatic tissue, miR-155 abundance and beta cell spatial/subcellular distribution were altered in donors with AAb⁺and type 1 diabetes compared with non-diabetic control individuals. Functionally, beta cell-targeted inhibition of miR-155 improved glucose tolerance and reduced insulitis in prediabetic NOD mice. Conclusions/interpretationUsing an organ-based model system of inflammatory stress, we validated a signature of EV-associated miRNAs capable of stratifying type 1 diabetes risk. Furthermore, we provided new mechanistic and imaging insights into miRNA expression patterns in pancreatic sections from human organ donors with type 1 diabetes or AAb⁺, and we used a preclinical model of type 1 diabetes to demonstrate the potential therapeutic efficacy of targeting these miRNAs. Data availabilityThe data from small RNA sequencig of human islets and islet-derived EVs have been deposited in the GEO database (accession no. GSE160391). 

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3. Differentially expressed microRNAs in brains of adult females may regulate the maternal block of diapause in Sarcophaga bullata

   https://doi.org/10.1016/j.cris.2024.100099  

   Reynolds, Julie A; Waight, Emma M (January 2024, Current Research in Insect Science)

   The maternal regulation of diapause is one type of phenotypic plasticity where the experience of the mother leads to changes in the phenotype of her offspring that impact how well-suited they will be to their future environment. Sarcophaga bullata females with a diapause history produce offspring that cannot enter diapause even if they are reared in a diapause inducing environment. Accumulating evidence suggests that microRNAs regulate diapause and, possibly, maternal regulation of diapause. We found significant differences in the abundances of several microRNAs (miR-125–5p, miR-124–3p, miR-31–5p, and miR-277–3p) in brains dissected from adult female S. bullata that had experienced diapause compared to females with no diapause history. We also found moderate differences in the mRNA expression of the circadian-clock related genes, clock, clockwork orange, and period. MiR-124–3p and miR-31–5p are part of a gene network that includes these circadian clock-related genes. Taken together our results suggest the maternal block of diapause in S. bullata is regulated, at least in part, by a network that includes microRNAs and the circadian clock. 

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4. MicroRNA Expression Prior to Biting in a Vector Mosquito Anticipates Physiological Processes Related to Energy Utilization, Reproduction and Immunity

   https://doi.org/10.3390/insects14080700  

   Marzec, Sarah; Siperstein, Alden; Zhou, Angela; Holzapfel, Christina; Bradshaw, William; Meuti, Megan; Armbruster, Peter (August 2023, Insects)

   Understanding the molecular and physiological processes underlying biting behavior in vector mosquitoes has important implications for developing novel strategies to suppress disease transmission. Here, we conduct small-RNA sequencing and qRT-PCR to identify differentially expressed microRNAs (miRNAs) in the head tissues of two subspecies of Culex pipiens that differ in biting behavior and the ability to produce eggs without blood feeding. We identified eight differentially expressed miRNAs between biting C. pipiens pipiens (Pipiens) and non-biting C. pipiens molestus (Molestus); six of these miRNAs have validated functions or predicted targets related to energy utilization (miR8-5-p, miR-283, miR-2952-3p, miR-1891), reproduction (miR-1891), and immunity (miR-2934-3p, miR-92a, miR8-5-p). Although miRNAs regulating physiological processes associated with blood feeding have previously been shown to be differentially expressed in response to a blood meal, our results are the first to demonstrate differential miRNA expression in anticipation of a blood meal before blood is actually imbibed. We compare our current miRNA results to three previous studies of differential messenger RNA expression in the head tissues of mosquitoes. Taken together, the combined results consistently show that biting mosquitoes commit to specific physiological processes in anticipation of a blood meal, while non-biting mosquitoes mitigate these anticipatory costs. 

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5. High Daytime Temperature Responsive MicroRNA Profiles in Developing Grains of Rice Varieties with Contrasting Chalkiness

   https://doi.org/10.3390/ijms241411631  

   Payne, David; Li, Yongfang; Govindan, Ganesan; Kumar, Anuj; Thomas, Julie; Addo-Quaye, Charles A.; Pereira, Andy; Sunkar, Ramanjulu (July 2023, International Journal of Molecular Sciences)

   High temperature impairs starch biosynthesis in developing rice grains and thereby increases chalkiness, affecting the grain quality. Genome encoded microRNAs (miRNAs) fine-tune target transcript abundances in a spatio-temporal specific manner, and this mode of gene regulation is critical for a myriad of developmental processes as well as stress responses. However, the role of miRNAs in maintaining rice grain quality/chalkiness during high daytime temperature (HDT) stress is relatively unknown. To uncover the role of miRNAs in this process, we used five contrasting rice genotypes (low chalky lines Cyp, Ben, and KB and high chalky lines LaGrue and NB) and compared the miRNA profiles in the R6 stage caryopsis samples from plants subjected to prolonged HDT (from the onset of fertilization through R6 stage of caryopsis development). Our small RNA analysis has identified approximately 744 miRNAs that can be grouped into 291 families. Of these, 186 miRNAs belonging to 103 families are differentially regulated under HDT. Only two miRNAs, Osa-miR444f and Osa-miR1866-5p, were upregulated in all genotypes, implying that the regulations greatly varied between the genotypes. Furthermore, not even a single miRNA was commonly up/down regulated specifically in the three tolerant genotypes. However, three miRNAs (Osa-miR1866-3p, Osa-miR5150-3p and canH-miR9774a,b-3p) were commonly upregulated and onemiRNA (Osa-miR393b-5p) was commonly downregulated specifically in the sensitive genotypes (LaGrue and NB). These observations suggest that few similarities exist within the low chalky or high chalky genotypes, possibly due to high genetic variation. Among the five genotypes used, Cypress and LaGrue are genetically closely related, but exhibit contrasting chalkiness under HDT, and thus, a comparison between them is most relevant. This comparison revealed a general tendency for Cypress to display miRNA regulations that could decrease chalkiness under HDT compared with LaGrue. This study suggests that miRNAs could play an important role in maintaining grain quality in HDT-stressed rice. 

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