miRNA-mediated Regulatory Networks Research Articles

Age-Related sncRNAs in Human Hippocampal Tissue Samples: Focusing on Deregulated miRNAs.

Small non-coding RNAs (sncRNAs), particularly microRNAs (miRNAs), play an important role in transcriptome regulation by binding to mRNAs and post-transcriptionally inhibiting protein production. This regulation occurs in both physiological and pathological conditions, where the expression of many miRNAs is altered. Previous reports by our group and others have demonstrated that miRNA expression is also altered during aging. However, most studies have analyzed human peripheral blood samples or brain samples from animal models, leaving a gap in knowledge regarding miRNA expression in the human brain. In this work, we analyzed the expression of sncRNAs from coronal sections of human hippocampal samples, a tissue with a high vulnerability to deleterious conditions such as aging. Samples from young (n = 5, 27-49 years old), old (n = 8, 58-88 years old), and centenarian (n = 3, 97, 99, and 100 years old) individuals were included. Our results reveal that sncRNAs, particularly miRNAs, are differentially expressed (DE) in the human hippocampus with aging. Besides, miRNA-mediated regulatory networks revealed significant interactions with mRNAs deregulated in the same hippocampal samples. Surprisingly, 80% of DE mRNA in the centenarian vs. old comparison are regulated by hsa-miR-192-5p and hsa-miR-3135b. Additionally, validated hsa-miR-6826-5p, hsa-let-7b-3p, hsa-miR-7846, and hsa-miR-451a emerged as promising miRNAs that are deregulated with aging and should be further investigated.

Dysregulation of miRNAs in Soft Tissue Sarcomas.

MicroRNAs (miRNAs) are pivotal regulators of gene expression, influencing key cellular processes such as proliferation, differentiation, apoptosis, and metastasis. In the realm of sarcomas-a diverse group of malignant tumors affecting soft tissues and bone sarcomas-miRNAs have emerged as crucial players in tumorigenesis and tumor progression. This review delves into the intricate roles of miRNAs across various soft tissue sarcoma subtypes, including rhabdomyosarcoma, liposarcoma, leiomyosarcoma, synovial sarcoma, fibrosarcoma, angiosarcoma, undifferentiated pleomorphic sarcoma (UPS), and malignant peripheral nerve sheath tumor (MPNST). We explore how dysregulated miRNAs function as oncogenes or tumor suppressors, modulating critical pathways that define the aggressive nature of these cancers. Furthermore, we discuss the diagnostic and prognostic potential of specific miRNAs and highlight their promise as therapeutic targets. By understanding the miRNA-mediated regulatory networks, this review aims to provide a comprehensive overview of current research while pointing towards future directions for miRNA-based therapies. Our findings underscore the potential of miRNAs to transform the landscape of sarcoma treatment, offering hope for more precise, personalized, and effective therapeutic strategies.

MicroRNAs in metabolic dysfunction-associated diseases: Pathogenesis and therapeutic opportunities.

Metabolic dysfunction-associated diseases often refer to various diseases caused by metabolic problems such as glucose and lipid metabolism disorders. With the improvement of living standards, the increasing prevalence of metabolic diseases has become a severe public health problem, including metabolic dysfunction-associated steatotic liver disease (MASLD), alcohol-related liver disease (ALD), diabetes and obesity. These diseases are both independent and interdependent, with complex and diverse molecular mechanisms. Therefore, it is urgent to explore the molecular mechanisms and find effective therapeutic targets of these diseases. MicroRNAs (miRNAs) have emerged as key regulators of metabolic homoeostasis due to their multitargets and network regulatory properties within the past few decades. In this review, we discussed the latest progress in the roles of miRNA-mediated regulatory networks in the development and progression of MASLD, ALD, diabetes and obesity.

Role of miRNAs in the Chikungunya virus replication and pathogenesis

Chikungunya virus (CHIKV) is a vector-born alphavirus responsible for chikungunya fever with clinical manifestation of polyarthritis transmitted by Aedes aegypti and Aedes albopictus. Establishing viral pathogenesis needs host machinery modulation, and the microRNAs (miRNA) modulate host cellular machinery to establish the infection or inhibit viral replication. miRNAs are the small noncoding RNA that control the gene expression. They are essential in cell differentiation, growth, development, and apoptosis. It also affects disease progression, cancer, and viral infection. CHIKV infection causes differential expression of miRNA, and miRNA has target genes involved in different cellular functions. These target genes may be crucial in CHIKV replication and cell growth. Suppression or overexpression of these miRNAs may have been linked with CHIKV pathogenesis by regulating immune and signaling pathways. Identification of biomarkers in disease progression through the study of circulating miRNAs during CHIKV infection is an emerging field. Therefore, understanding miRNAs’ differential expression and function during CHIKV infection is essential. The detailed studies on the miRNA-mediated regulatory network will provide new ways to develop miRNA-based therapies.

Combinatorial microRNA activity is essential for the transition of pluripotent cells from proliferation into dormancy.

Dormancy is a key feature of stem cell function in adult tissues as well as in embryonic cells in the context of diapause. The establishment of dormancy is an active process that involves extensive transcriptional, epigenetic, and metabolic rewiring. How these processes are coordinated to successfully transition cells to the resting dormant state remains unclear. Here we show that microRNA activity, which is otherwise dispensable for preimplantation development, is essential for the adaptation of early mouse embryos to the dormant state of diapause. In particular, the pluripotent epiblast depends on miRNA activity, the absence of which results in the loss of pluripotent cells. Through the integration of high-sensitivity small RNA expression profiling of individual embryos and protein expression of miRNA targets with public data of protein-protein interactions, we constructed the miRNA-mediated regulatory network of mouse early embryos specific to diapause. We find that individual miRNAs contribute to the combinatorial regulation by the network, and the perturbation of the network compromises embryo survival in diapause. We further identified the nutrient-sensitive transcription factor TFE3 as an upstream regulator of diapause-specific miRNAs, linking cytoplasmic MTOR activity to nuclear miRNA biogenesis. Our results place miRNAs as a critical regulatory layer for the molecular rewiring of early embryos to establish dormancy.

Joint Analysis of Small RNA and mRNA Sequencing Unveils miRNA-Mediated Regulatory Network in Response to Methyl Jasmonate in Apocynum venetum L.

Apocynum venetum L. is a natural fiber and medicinal plant species with significant economic value. Jasmonic acid is an endogenous growth regulatory substance present in higher plants that participate in plant growth, development, and defense. As important endogenous single-stranded RNA molecules, microRNA (miRNA) plays an important role in the post-transcriptional regulation of plant genes. A combination of miRNA and mRNA sequencing techniques was used to systematically identify the methyl jasmonate miRNAs and mRNAs in A. venetum. Up to 135 conserved and 26 species-specific miRNAs have been identified in A. venetum. These miRNAs mainly target genes that encode transcription factors and enzymes. The expression levels of 23 miRNAs, including miR398 and miR482, significantly changed after MeJA treatment. A total of 1778 genes were differentially expressed under MeJA treatment, of which 825 were upregulated and 953 were downregulated. The main biological processes enriched in these differentially expressed genes were redox balance, secondary metabolism, photosynthesis, and plant hormone signal transduction. Joint analysis of the miRNAs and mRNA revealed that MeJA-responsive miRNAs function by forming regulatory modules, including miR398-CSD, miR482-NBS-LRR, miR156-SPL10, and miR164-NAC056, which further regulate multiple biological processes, including redox balance, disease resistance, and morphogenesis in A. venetum. This study provides important information to understand the biological roles of miRNAs in A. venetum.

Integrated transcriptome and small RNA sequencing revealing miRNA-mediated regulatory network of bicolour pattern formation in Pericallis hybrida ray florets

Flower spots of plants are of evolutionary importance and ornamental value, but research on regulatory mechanisms is still limited. Cineraria (Pericallis hybrida) is an important ornamental plant with various bicolour cultivars. In this study, we performed transcriptome and small RNA sequencing to investigate the regulatory network of bicolour pattern formation in P. hybrida ray florets. Through transcriptome sequencing, we mainly focused on differentially expressed genes (DEGs) involved in flavonoid biosynthesis. Gene expression analysis showed that PhLAR (Unigene0092951), PhMYB8 (Unigene0068595) and PhbHLH137 (Unigene0091507) were up-regulated in the colourless region. Additionally, we identified 234 known miRNAs and 280 novel miRNAs by sRNA sequencing, and 49 differentially expressed miRNAs (DEmiRs) were screened. Integrated analysis of RNA-seq and sRNA-seq data revealed that miR172-AP2 and miR156-SPL modules were crucial in regulating bicolour pattern formation. When PhAP2 was transiently silenced in cineraria capitulum by virus-induced gene silencing (VIGS), the colourless region of ray florets increased and the coloured region changed from carmine to pink. Meanwhile, PhCHS2, PhDFR3 and PhANS were down-regulated, while PhLAR was up-regulated significantly. It was hypothesized that PhAP2 functions as an inhibitor of bicolour pattern appearance and could influence flavonoid biosynthesis. Overall, our study revealed a possible regulatory network of miRNA-mediated bicolour pattern appearance in P. hybrida, which could enrich the post-transcriptional regulatory mechanisms of flower spots formation in ornamental plants.

MiProBERT: identification of microRNA promoters based on the pre-trained model BERT.

Accurate prediction of promoter regions driving miRNA gene expression has become a major challenge due to the lack of annotation information for pri-miRNA transcripts. This defect hinders our understanding of miRNA-mediated regulatory networks. Some algorithms have been designed during the past decade to detect miRNA promoters. However, these methods rely on biosignal data such as CpG islands and still need to be improved. Here, we propose miProBERT, a BERT-based model for predicting promoters directly from gene sequences without using any structural or biological signals. According to our information, it is the first time a BERT-based model has been employed to identify miRNA promoters. We use the pre-trained model DNABERT, fine-tune the pre-trained model on the gene promoter dataset so that the model includes information about the richer biological properties of promoter sequences in its representation, and then systematically scan the upstream regions of each intergenic miRNA using the fine-tuned model. About, 665 miRNA promoters are found. The innovative use of a random substitution strategy to construct a negative dataset improves the discriminative ability of the model and further reduces the false positive rate (FPR) to as low as 0.0421. On independent datasets, miProBERT outperformed other gene promoter prediction methods. With comparison on 33 experimentally validated miRNA promoter datasets, miProBERT significantly outperformed previously developed miRNA promoter prediction programs with 78.13% precision and 75.76% recall. We further verify the predicted promoter regions by analyzing conservation, CpG content and histone marks. The effectiveness and robustness of miProBERT are highlighted.

A novel miRNA, Cse-miR-33, functions as an immune regulator by targeting CsTRAF6 in Chinese tongue sole (Cynoglossus semilaevis)

The tumor necrosis factor receptor-associated factor 6 (TRAF6) can act as a fundamental adaptor protein in a chain reaction of signal transduction and cascade events to finish off immune defenses. However, immunomodulatory research on TRAF6 gene is still limited in fish. In this study, a novel miRNA, Cse-miR-33 was identified from the whole genome of Chinese tongue sole (Cynoglossus semilaevis). After separate infections with three different Vibrio strains (V. harveyi, V. anguillarum, V. parahemolyticus) and one virus (nervous necrosis virus, NNV), the expressions of CsTRAF6 and Cse-miR-33 displayed significant time-dependent changes in immune related tissues and the trends were opposite in general. Through target gene prediction and dual luciferase reporter assay, Cse-miR-33 was proven to regulate CsTRAF6 by combining with 3′-UTR sequence of the gene. The results of qRT-PCR and western blotting (WB) analyses showed that Cse-miR-33 blocked the translation of CsTRAF6 protein at post-transcriptional level, rather than degrading the target mRNA. Further experiment indicated that Cse-miR-33 inhibitor largely reduced the death rate of Chinese tongue sole caused by V. harveyi and NNV. The expressions of CsTRAF6-associated immune genes (such as CsIL-1R, CsMYD88, CsIRAK1, CsTNFα, CsIL6 and CsIL8) were also significantly changed in response to Cse-miR-33 agomir and inhibitor. The study suggested that Cse-miR-33 affected the immune response via targeting CsTRAF6 in C. semilaevis, which would provide us deep insights into miRNA-mediated regulatory network and help improve the immunity in fish.

Identification of Nitrogen Starvation-Responsive miRNAs to Reveal the miRNA-Mediated Regulatory Network in Betula luminifera.

Because of the immobility, plants encounter a series of stresses, such as varied nutrient concentrations in soil, which regulate plant growth, development, and phase transitions. Nitrogen (N) is one of the most limiting factors for plants, which was exemplified by the fact that low nitrogen (LN) has a great adverse effect on plant growth and development. In the present study, we explored the potential role of microRNAs (miRNAs) in response to LN stress in Betula luminifera. We identified 198 miRNAs using sRNA sequencing, including 155 known and 43 novel miRNAs. Among them, 98 known miRNAs and 31 novel miRNAs were differentially expressed after 0.5 h or 24 h of LN stress. Based on degradome data, 122 differential expressed miRNAs (DEmiRNAs) including 102 known miRNAs and 20 novel miRNAs targeted 203 genes, comprising 321 miRNA–target pairs. A big proportion of target genes were transcription factors and functional proteins, and most of the Gene Ontology terms were enriched in biological processes; moreover, one Kyoto Encyclopedia of Genes and Genomes term “ascorbate and aldarate metabolism” was significantly enriched. The expression patterns of six miRNAs and their corresponding target genes under LN stress were monitored. According to the potential function for targets of DEmiRNAs, a proposed regulatory network mediated by miRNA–target pairs under LN stress in B. luminifera was constructed. Taken together, these findings provide useful information to elucidate miRNA functions and establish a framework for exploring N signaling networks mediated by miRNAs in B. luminifera. It may provide new insights into the genetic engineering of the high use efficiency of N in forestry trees.

Integrated transcriptome and small RNA sequencing in revealing miRNA-mediated regulatory network of floral bud break in Prunus mume.

MicroRNAs is one class of small non-coding RNAs that play important roles in plant growth and development. Though miRNAs and their target genes have been widely studied in many plant species, their functional roles in floral bud break and dormancy release in woody perennials is still unclear. In this study, we applied transcriptome and small RNA sequencing together to systematically explore the transcriptional and post-transcriptional regulation of floral bud break in P. mume. Through expression profiling, we identified a few candidate genes and miRNAs during different developmental stage transitions. In total, we characterized 1,553 DEGs associated with endodormancy release and 2,084 DEGs associated with bud flush. Additionally, we identified 48 known miRNAs and 53 novel miRNAs targeting genes enriched in biological processes such as floral organ morphogenesis and hormone signaling transudation. We further validated the regulatory relationship between differentially expressed miRNAs and their target genes combining computational prediction, degradome sequencing, and expression pattern analysis. Finally, we integrated weighted gene co-expression analysis and constructed miRNA-mRNA regulatory networks mediating floral bud flushing competency. In general, our study revealed the miRNA-mediated networks in modulating floral bud break in P. mume. The findings will contribute to the comprehensive understanding of miRNA-mediated regulatory mechanism governing floral bud break and dormancy cycling in wood perennials.

Genome-wide identification, classification and expression analysis of the JmjC domain-containing histone demethylase gene family in Jatropha curcas L.

JmjC domain-containing proteins, an important family of histone lysine demethylase, play significant roles in maintaining the homeostasis of histone methylation. In this study, we comprehensively analyzed the JmjC domain-containing gene family in Jatropha curcas and found 20 JmjC domain-containing genes (JcJMJ genes). Phylogenetic analysis revealed that these JcJMJ genes can be classified into five major subgroups, and genes in each subgroup had similar motif and domain composition. Cis-regulatory element analysis showed that the number and types of cis-regulatory elements owned by the promoter of JcJMJ genes in different subgroup were significantly different. Moreover, miRNA target prediction result revealed a complicated miRNA-mediated post-transcriptional regulatory network, in which JcJMJ genes were regulated by different numbers and types of miRNAs. Further analysis of the tissue and stress expression profiles showed that many JcJMJ genes had tissue and stress expression specificity. All these results provided valuable information for understanding the evolution of JcJMJ genes and the complex transcriptional and post transcriptional regulation involved, and laid the foundation for further functional analysis of JcJMJ genes.

Comprehensive Analysis of miRNA-Mediated Regulatory Network and Identification of Prognosis Biomarkers in Rectal Cancer.

Rectal cancer is a malignant tumor with poor prognosis. Identification of prognostic biomarkers is needed to improve overall survival of rectal cancer patients. Here, we firstly identified miR-20a-5p significantly classifying high-risk group and low-risk group of rectal cancer patients. We also found that several known miRNAs miR-142-5p, miR-486-5p, miR-490-3p and miR-133a-3p played important roles in rectal cancer. Secondly, we constructed and analyzed a rectal cancer-related miRNA-mRNA network. A rectal cancer-related functional module was identified from the miRNA-mRNA network. Survival analysis demonstrated great prognosis capacity of the module to distinguish rectal cancer patients. Thirdly, a rectal cancer-related miRNA-lncRNA network was constructed, which followed power law distribution. Hub miRNAs and lncRNAs of the network were suggested to show significant prognosis ability and be enriched in cancer-related pathways. Fourthly, we constructed a rectal cancer-related ceRNA network and detected several typical lncRNA-miRNA-mRNA crosstalk, such as HAND2-AS1, HAND2 and miR-20a-5p crosstalk and MBNL1-AS1, miR-429 and LONRF2 crosstalk, which were validated to function in improving overall survival of rectal cancer patients. Finally, we identified the regulatory feedback that was constituted by transcriptional factors and lncRNAs, including MEIS1, MEIS2 and multiple lncRNAs. We also demonstrated that these lncRNAs were high related to immune cell infiltration. All these results can help us to uncover the molecular mechanism and provide new light on miRNA-mediated gene crosstalks in rectal cancer.

MicroRNA-106b-5p Promotes Cell Growth and Sensitizes Chemosensitivity to Sorafenib by Targeting the BTG3/Bcl-xL/p27 Signaling Pathway in Hepatocellular Carcinoma.

microRNAs (miRNAs) and miRNA-mediated regulatory networks are promising candidates in the prevention and treatment of cancer, but the role of specific miRNAs involved in hepatocellular carcinoma (HCC) remains to be elusive. Herein, we found that miR-106b-5p is upregulated in both HCC patients' tumor tissues and HCC cell lines. The miR-106b-5p expression level was positively correlated with α-fetoprotein (AFP), hepatitis B surface antigen (HBsAg), and tumor size. Overexpression of miR-106b-5p promoted cell proliferation, migration, cell cycle G1/S transition, and tumor growth, while decreased miR-106b-5p expression had opposite effects. Mechanistic studies showed that B-cell translocation gene 3 (BTG3), a known antiproliferative protein, was a direct target of miR-106b-5p, whose expression level is inversely correlated with miR-106b-5p expression. Moreover, miR-106b-5p positively regulates cell proliferation in a BTG3-dependent manner, resulting in upregulation of Bcl-xL, cyclin E1, and CDK2, as well as downregulation of p27. More importantly, we also demonstrated that miR-106b-5p enhances the resistance to sorafenib treatment in a BTG3-dependent manner. The in vivo findings showed that mice treated with a miR-106b-5p sponge presented a smaller tumor burden than controls, while the mice injected cells treated with miR-106b-5p had more considerable tumor burden than controls. Altogether, these data suggest that miR-106b-5p promotes cell proliferation and cell cycle and increases HCC cells' resistance to sorafenib through the BTG3/Bcl-xL/p27 signaling pathway.

Identification and differential expression of microRNAs in Madin-Darby canine kidney cells with high and low tumorigenicities.

Madin-Darby canine kidney (MDCK) cells are widely used for vaccine production, however, the safety of MDCK cells needs to be considered seriously because of high tumorigenicity. Micro RNAs (miRNAs) that are involved in the tumorigenicity of MDCK cells have been never been reported. To reveal the role of miRNA in the tumorigenic phenotype of MDCK cell line. The miRNA expression profiles of two monoclonal MDCK cells (M09CL and M35CL) with low tumorigenicity and one MDCK cell line (M73P) with high tumorigenicity were characterized and investigated by using small RNA-seq technology. A total of 5 known miRNAs and 5 novel miRNAs were highly expressed in M73P. In addition, 4 known miRNAs and 4 novel miRNAs were highly expressed in M09CL and M35CL. The target genes of the differentially expressed miRNAs were significantly enriched in several biological processes, and the majority of these genes were involved in pathways in cancer and the MAPK signaling pathway. Through interaction analysis, 4 up-regulated miRNAs (cfa-miR-452, cfa-miR-8826, cfa-miR-224, and cfa-miR-2387) and their crucial target genes related to the tumor regulation network were identified. Results indicated these 4 miRNAs might play crucial roles in the tumorigenesis of MDCK cells. Our findings, which were based on the functional prediction of miRNAs and target genes, suggested that miRNAs might influence the tumorigenicity of MDCK cells by regulating target genes. Moreover, the results provided important data for understanding the miRNA-mediated regulatory networks that control the tumorigenicities of MDCK cells.

Identification and characterization of heat-responsive miRNAs and their regulatory network in maize

MicroRNAs (miRNAs) are small non-coding RNAs that play essential functions in abiotic stress responses. High temperature is a serious stress that affects crop yield and quality; however, the regulatory mechanisms of heat-responsive miRNAs remain poorly understood in maize (Zea mays L.). Here, 340 miRNAs (215 known and 125 novel) were identified from maize seedlings under heat stress and control conditions using high-throughput sequencing in elite inbred line CM1. The 215 known miRNAs were divided into 40 families, and 21-nt miRNAs were the most abundant. In total, 35 miRNAs (26 known and 9 novel) exhibited significantly different expression levels between the heat stress and control samples. Furthermore, 174 targets were predicted to be cleaved by 115 miRNAs using degradome sequencing. The biological roles and pathways of these targets were investigated using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. On the basis of relationships among miRNAs and target genes, as well as the enrichment results, a regulatory network was constructed, and 16 significantly differentially expressed miRNAs were involved in the network. Our study shows a comprehensive analysis of heat-responsive miRNAs and their targets in the maize inbred line CM1. The results are helpful for the functional research of the heat stress responsive miRNAs, and provide novel insights into the miRNA-mediated regulatory network and the underlying mechanisms in maize during heat stress response.

MicroRNA-Mediated Gene Regulation of Secondary Metabolism in Plants

Plant microRNAs (miRNAs), a class of about 21-nucleotide-long small noncoding RNAs (ncRNAs), generally act as key regulators of their target genes by guiding mRNA cleavage or translational repression. Recent researches have reported that miRNAs can interact with pathway-related structural genes, transcription factors (TFs) and noncoding RNAs (ncRNAs) to form regulatory network in secondary metabolite (SM) biosynthetic pathways. The validated interactions can better reflect the real regulatory mechanism of miRNA and convert miRNAs into more efficient tools to control the production of precious SMs. However, there is no systematic review available on this topic especially in plants, particularly model plants and crops. Here, we firstly overviewed the critical secondary metabolic pathways in plants, especially those biosynthetic pathways related structural genes which were well-studied and representative SMs, including phenylpropanoids, terpenoids, alkaloids. Principally, we summarized miRNAs involved in the biosynthesis of SMs, miRNA-target modules and their regulation on the mentioned pathways in the last decade. Significantly, the modules included miRNA-structural gene, miRNA-TF, miRNA-ncRNA interaction pairs carried out by target validation or functional confirmation. This knowledge will promote understanding the sophisticated miRNA-mediated gene regulatory network of SM biosynthesis, and drive the development of synthetic biology.

Identification of novel drought-responsive miRNA regulatory network of drought stress response in common vetch (Vicia sativa).

Drought is among the most important natural disasters with severe effects on animals and plants. MicroRNAs are a class of noncoding RNAs that play a crucial role in plant growth, development, and response to stress factors, including drought. However, the microRNAs in drought responses in common vetch (Vicia sativa), an annual herbaceous leguminous plant commonly used for forage by including it in mixed seeding during winter and spring, have not been characterized. To explore the microRNAs’ response to drought in common vetch, we sequenced 10 small RNA (sRNA) libraries by the next-generation sequencing technology. We obtained 379 known miRNAs belonging to 38 families and 47 novel miRNAs. The two groups had varying numbers of differentially expressed miRNAs: 85 in the comparison group D5 vs C5 and 38 in the comparison group D3 vs C3. Combined analysis of mRNA and miRNA in the same samples under drought treatment identified 318 different target genes of 123 miRNAs. Functional annotation of the target genes revealed that the miRNAs regulate drought-responsive genes, such as leucine-rich repeat receptor-like kinase-encoding genes (LRR-RLKs), ABC transporter G family member 1 (ABCG1), and MAG2-interacting protein 2 (MIP2). The genes were involved in various pathways, including cell wall biosynthesis, reactive oxygen removal, and protein transport. The findings in this study provide new insights into the miRNA-mediated regulatory networks of drought stress response in common vetch.

MicroRNAs, the Link Between Dengue Virus and the Host Genome.

Dengue virus (DENV) is a small envelope virus of Flaviviridae that is mainly transmitted by Aedes aegypti and Aedes albopictus. It can cause dengue fever with mild clinical symptoms or even life-threatening dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). At present, there are no specific drugs or mature vaccine products to treat DENV. microRNAs (miRNAs) are a class of important non-coding small molecular RNAs that regulate gene expression at the post-transcriptional level. It is involved in and regulates a series of important life processes, such as growth and development, cell differentiation, cell apoptosis, anti-virus, and anti-tumor. miRNAs also play important roles in interactions between host and viral genome transcriptomes. Host miRNAs can directly target the genome of the virus or regulate host factors to promote or inhibit virus replication. Understanding the expression and function of miRNAs during infection with DENV and the related signal molecules of the miRNA-mediated regulatory network will provide new insights for the development of miRNA-based therapies.

Characterizing microRNA-mediated modulation of gene expression noise and its effect on synthetic gene circuits.

MicroRNAs (miRNAs) have been shown to modulate gene expression noise, but less is known about how miRNAs with different properties may regulate noise differently. Here, we investigate the role of competing RNAs and the composition of miRNA response elements (MREs) in modulating noise. We find that weak competing RNAs could introduce lower noise than strong competing RNAs. In comparison with a single MRE, both repetitive and composite MREs can reduce the noise at low expression, but repetitive MREs can elevate the noise remarkably at high expression. We further observed the behavior of a synthetic cell-type classifier with miRNAs as inputs and find that miRNAs and MREs that could introduce higher noise tend to enhance cell state transition. These results provide a systematic and quantitative understanding of the function of miRNAs in controlling gene expression noise and the utilization of miRNAs to modulate the behavior of synthetic gene circuits.