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MiRNAs are assumed to be important in animal development and physiology, but their specific roles in vivo are still poorly understood. New bioinformatic and genetic studies are setting the stage for unraveling the specific biological functions of miRNAs.
MicroRNAs, small noncoding RNAs, are implicated in gene regulation in both metazoans and plants. In plants, many of the targets of miRNA-mediated gene regulation encode transcription factors with functions in development, such as the Class III HD-Zip gene family whose members direct polarity establishment in leaves and vasculature. Three recent papers provide insight into how miRNAs, likely acting through a complex containing an Argonaute protein, regulate Class III HD-Zip gene expression in Arabidopsis and maize.1-3 While the precise biological activity of Argonaute proteins remains an enigma, ARGONAUTE1 in Arabidopsis is required for the proper regulation of miRNA165/166, which targets cleavage of Class III HD-Zip mRNAs. Consistent with their proposed role in negative regulation, expression of miRNA165/166 is complementary to that of Class III HD-Zip gene expression, but this is perturbed in agronaute1 mutants. Determining how these complementary patterns of expression are formed should lead us closer to an understanding of the molecular mechanisms by which asymmetry is established in developing leaves.
MOTIVATION: Most non-coding RNAs are characterized by a specific secondary and tertiary structure that determines their function. Here, we investigate the folding energy of the secondary structure of non-coding RNA sequences, such as microRNA precursors, transfer RNAs and ribosomal RNAs in several eukaryotic taxa. Statistical biases are assessed by a randomization test, in which the predicted minimum free energy of folding is compared with values obtained for structures inferred from randomly shuffling the original sequences. RESULTS: In contrast with transfer RNAs and ribosomal RNAs, the majority of the microRNA sequences clearly exhibit a folding free energy that is considerably lower than that for shuffled sequences, indicating a high tendency in the sequence towards a stable secondary structure. A possible usage of this statistical test in the framework of the detection of genuine miRNA sequences is discussed.
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MicroRNAs represent a class of short (approximately 22 nt), noncoding regulatory RNAs involved in development, differentiation, and metabolism. We describe a novel microarray platform for genome-wide profiling of mature miRNAs (miChip) using locked nucleic acid (LNA)-modified capture probes. The biophysical properties of LNA were exploited to design probe sets for uniform, high-affinity hybridizations yielding highly accurate signals able to discriminate between single nucleotide differences and, hence, between closely related miRNA family members. The superior detection sensitivity eliminates the need for RNA size selection and/or amplification. MiChip will greatly simplify miRNA expression profiling of biological and clinical samples.
We describe here a new method for highly efficient detection of microRNAs by northern blot analysis using LNA (locked nucleic acid)-modified oligonucleotides. In order to exploit the improved hybridization properties of LNA with their target RNA molecules, we designed several LNA-modified oligonucleotide probes for detection of different microRNAs in animals and plants. By modifying DNA oligonucleotides with LNAs using a design, in which every third nucleotide position was substituted by LNA, we could use the probes in northern blot analysis employing standard end-labelling techniques and hybridization conditions. The sensitivity in detecting mature microRNAs by northern blots was increased by at least 10-fold compared to DNA probes, while simultaneously being highly specific, as demonstrated by the use of different single and double mismatched LNA probes. Besides being highly efficient as northern probes, the same LNA-modified oligonucleotide probes would also be useful for miRNA in situ hybridization and miRNA expression profiling by LNA oligonucleotide microarrays.
The discovery of micro-RNAs (miRNAs) and the growing appreciation of the importance of micro-RNAs in the regulation of gene expression are driving increasing interest in miRNA expression profiling. Early studies have suggested prominent roles for these genetically encoded regulatory molecules in a variety of normal biological processes and diseases, particularly cancer. However, the field of miRNA expression profiling is in its infancy. Several factors, including the small size, the unknown but limited number of miRNAs, and the tissue-to-tissue and tissue-to-disease state variability in miRNA expression, make the adaptation of microarray technology to the evaluation of miRNA expression nontrivial. This chapter describes the unique features of miRNA microarray experiments and analysis and provides a case study demonstrating our approach to miRNA expression analysis.
Plant and animal genomes contain an abundance of small genes that produce RNAs of about 22 nucleotides in length, which was dubbed as microRNAs. These newly found endogenous RNAs may participate in a wide range of genetic regulatory pathways and play an important role in the development. This paper is focused on the finding of the microRNAs, its mechanism and function, as well as the methods of research.
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The role of small RNAs as key regulators of mRNA turnover and translation has been well established. Recent advances indicate that the small RNAs termed microRNAs play important roles in cell proliferation, apoptosis and differentiation. Moreover, the microRNA mechanism is an efficient means to regulate production of a diverse range of proteins. As new microRNAs and their mRNA targets rapidly emerge, it is becoming apparent that RNA-based regulation of mRNAs may rival ubiquitination as a mechanism to control protein levels.
MOTIVATION: Most computational methodologies for microRNA gene prediction utilize techniques based on sequence conservation and/or structural similarity. In this study we describe a new technique, which is applicable across several species, for predicting miRNA genes. This technique is based on machine learning, using the Naive Bayes classifier. It automatically generates a model from the training data, which consists of sequence and structure information of known miRNAs from a variety of species. RESULTS: Our study shows that the application of machine learning techniques, along with the integration of data from multiple species is a useful and general approach for miRNA gene prediction. Based on our experiments, we believe that this new technique is applicable to an extensive range of eukaryotes' genomes. Specific structure and sequence features are first used to identify miRNAs followed by a comparative analysis to decrease the number of false positives (FPs). The resulting algorithm exhibits higher specificity and similar sensitivity compared to currently used algorithms that rely on conserved genomic regions to decrease the rate of FPs.
MicroRNAs are small non-coding RNAs of 19-24 nucleotides in length that downregulate gene expression during various crucial cell processes such as apoptosis, differentiation and development. Recent work supports a role for miRNAs in the initiation and progression of human malignancies. Large high-throughput studies in patients revealed that miRNA profiling have the potential to classify tumors with high accuracy and predict outcome. Functional studies, some of which involve animal models, indicate that miRNAs act as tumor suppressors and oncogenes. Here, we summarize miRNA-profiling studies in human malignancies and examine the role of miRNAs in the pathogenesis of cancer. We also discuss the implications of these findings for the diagnosis and treatment of cancer.
Micro RNAs comprise a large family of small, functional RNAs with important roles in the regulation of protein coding genes in animals and plants. Here we show that human and mouse miRNA22 precursor molecules are subject to posttranscriptional modification by A-to-I RNA editing in vivo. The observed editing events are predicted to have significant implications for the biogenesis and function of miRNA22 and might point toward a more general role for RNA editing in the regulation of miRNA gene expression.
Non-coding RNAs (ncRNAs) have been demonstrated to be involved in muscle development and to function as key regulators. However, the molecular mechanism underlying muscle crispiness in grass carp (GC) remains poorly understood, and whether these ncRNAs are involved in its regulation is still unknown. In the current investigation, differentially expressed (DE) RNAs (including lncRNAs, circRNAs, miRNAs, and mRNAs) were identified; concomitantly, target genes prediction was conducted, and functional and signaling pathway enrichment analyses were performed. Pathways related to muscle crispiness were identified, and the competitive endogenous RNA (ceRNA) (lncRNA/circRNA-miRNA-mRNA) regulatory network was further constructed. The results showed that a total of 126 DE-lncRNAs, 17 DE-circRNAs, 329 DE-miRNAs, and 442 DE-mRNAs were identified in muscle tissues of both the GC and crisp grass carp (CGC). GO and KEGG enrichment analyses revealed that target genes of DE-ncRNAs were significantly enriched in signaling pathways, including structural constituents of muscle, apoptosis, oxidative phosphorylation, and regulation of actin cytoskeleton, suggesting that these pathways may be involved in muscle texture remodeling. Subsequently, DE-RNAs enriched in related pathways were identified, and a core ceRNA regulation network comprising 3 lncRNAs, 4 circRNAs, 3 miRNAs, and 17 mRNAs was constructed. Additionally, 10 DE-RNAs from randomly selected groups were validated by qRT-PCR. Our findings not only provide scientific evidence elucidating the molecular mechanisms underlying muscle crispiness in GC but also establish a foundation for studying changes in muscle textural qualities across other fish species.
Pancreatic ductal adenocarcinoma (PDAC) remains a difficult tumor to diagnose and treat. To date, PDAC lacks routine screening with no markers available for early detection. Exosomes are 40-150 nm-sized extracellular vesicles that contain DNA, RNA, and proteins. These exosomes are released by all cell types into circulation and thus can be harvested from patient body fluids, thereby facilitating a non-invasive method for PDAC detection. A bioinformatics analysis was conducted utilizing publicly available miRNA pancreatic cancer expression and genome databases. Through this analysis, we identified 18 miRNA with strong potential for PDAC detection. From this analysis, 10 (MIR31, MIR93, MIR133A1, MIR210, MIR330, MIR339, MIR425, MIR429, MIR1208, and MIR3620) were chosen due to high copy number variation as well as their potential to differentiate patients with chronic pancreatitis, neoplasms, and PDAC. These 10 were examined for their mature miRNA expression patterns, giving rise to 18 mature miRs for further analysis. Exosomal RNA from cell culture media was analyzed via RTqPCR and seven mature miRs exhibited statistical significance (miR-31-5p, miR-31-3p, miR-210-3p, miR-339-5p, miR-425-5p, miR-425-3p, and miR-429). These identified biomarkers can potentially be used for early detection of PDAC.
Cytoplasmic processing bodies, or P-bodies, contain a high concentration of enzymes and factors required for mRNA turnover and translational repression. Recent studies provide evidence that the mRNAs silenced by miRNAs are localized to P-bodies for storage or degradation, perhaps in adjacent subcompartments. mRNP remodeling, potentially induced by miRISC or RNA helicase activity, may cause the modification of the translation initiation complex at the 5' end of mRNA, following translational repression and localization to P-bodies. Further remodeling in P-bodies may facilitate access of the decapping complex to the cap structure, thus inducing mRNA degradation. However, with appropriate signals, stored mRNAs in P-bodies could be released and returned to the translational machinery through mechanisms requiring binding of regulatory proteins to the 3' UTR of mRNAs. Here a model is proposed to explain the repression and degradation stages of the mRNAs within PBs. This model includes preservation or disruption of a stable closed loop structure of the mRNAs, compartmentalization in PBs and mRNA escape triggered by additional binding proteins.
Dengue infection is a mosquito-borne disease that can cause mild illness or severe haemorrhagic fever. Predictive biomarkers for severe cases, especially those with bleeding manifestations or plasma leakage, are currently lacking. This systematic review and meta-analysis synthesises findings from studies on circulating miRNAs in dengue infection, sourced from PubMed, Scopus, Science Direct, and Web of Science, with quality assessed by the Newcastle-Ottawa Scale (PROSPERO: CRD42024521685). Quantitative meta-analyses were conducted using RStudio to evaluate diagnostic Area Under the Curve (AUC) metrics across five eligible studies and Standardised Mean Differences (SMD) for differential miRNA expression. Key miRNAs, such as miR-146a, miR-150, miR-378, miR-21-5p, and miR-1246, were found to regulate immune responses, inflammation, and viral replication. Meta-analysis demonstrated high overall diagnostic accuracy for circulating miRNAs, with individual reported AUC values ranging from 0.79 to 1.00; however, substantial statistical heterogeneity was observed across pooled metrics (I-squared exceeding 89%). SMD analysis highlighted significant upregulation of acute inflammatory drivers, including miR-21-5p (SMD = 4.67) and miR-450b-5p (SMD = 6.76), alongside marked downregulation of endothelial-protective markers such as miR-126-3p (SMD = -1.31). Rather than viewing dysregulated microRNAs as a uniform class of clinical tools, this review highlights that candidate microRNAs span distinct translational tiers. Recognising these validation levels alongside pre-analytical and biological heterogeneity is essential for prioritising the most viable microRNA candidates for future prospective clinical translation and targeted therapies in dengue management.