Search Results (83)

Drought is a leading constraint on plant productivity and will intensify with climate change. Plant acclimation emerges from a multilayered regulatory system that integrates signaling, transcriptional reprogramming, RNA-based control, and chromatin dynamics. Within this hierarchy, non-coding RNAs (ncRNAs) provide a unifying regulatory layer; microRNAs (miRNAs) modulate abscisic acid and auxin circuits, oxidative stress defenses, and root architecture. This balances growth with survival under water-deficient conditions. Small interfering RNAs (siRNAs) include 24-nucleotide heterochromatic populations that operate through RNA-directed DNA methylation, which positions ncRNA control at the transcription–chromatin interface. Long non-coding RNAs (lncRNAs) act in cis and trans, interact with small RNA pathways, and can serve as chromatin-associated scaffolds. Circular RNAs (circRNAs) are increasingly being detected as responsive to drought. Functional studies in Arabidopsis and maize (e.g., ath-circ032768 and circMED16) underscore their regulatory potential. This review consolidates ncRNA biogenesis and function, catalogs drought-responsive modules across model and crop species, especially cereals, and outlines methodological priorities, such as long-read support for isoforms and back-splice junctions, stringent validation, and integrative multiomics. The evidence suggests that ncRNAs are tractable entry points for enhancing drought resilience while managing growth–stress trade-offs. Full article

Circular RNAs are a class of stable non-coding RNAs generated through a back-splicing mechanism. They are now recognized as central players in cell function and are no longer considered byproducts of transcription. CircRNAs regulate gene expression at the transcriptional, post-transcriptional, and translational levels by interacting with various molecules. They act as sponges for miRNAs and proteins, molecular scaffolds, and can also be translated into peptides. Although advances in next-generation sequencing and PCR methods have improved their identification and quantification, technical and bioinformatic challenges remain. Increasing evidence shows their involvement in cardiovascular diseases such as heart failure, hypertrophy, fibrosis, and atherosclerosis, with protective or deleterious effects depending on the context. Given their presence in biological fluids and extracellular vesicles, they can be considered promising biomarkers, but their therapeutic applications are still under investigation. Future studies including a better understanding of their mechanisms of action, the development of standardized validation methods, and potential clinical applications (prevention, early diagnosis, personalized therapies) in diseases are still needed. This review provides an updated overview of the knowledge regarding circRNAs and their translational role in health and disease with a particular focus on cardiovascular diseases. Full article

Breast cancer metastasis remains the primary driver of patient mortality, involving dynamic interactions between tumor cells and distant organ microenvironments. In recent years, tumor cell-derived extracellular vesicles (EVs) have emerged as critical information carriers, playing central roles in breast cancer metastasis by mediating organ-specific pre-metastatic niche formation, immune modulation, and tumor cell adaptive evolution. Studies have demonstrated that EVs drive the metastatic cascade through the delivery of bioactive components, including nucleic acids (e.g., miRNAs, circRNAs), proteins (e.g., integrins, metabolic enzymes), and lipids, which collectively regulate osteoclast activation, immune cell polarization, vascular permeability alterations, and extracellular matrix (ECM) remodeling in target organs such as bone, the lungs, and the liver. Molecular heterogeneity in EVs derived from different breast cancer subtypes strongly correlates with organotropism, providing potential biomarkers for metastasis prediction. Leveraging the organotrophic mechanisms of EVs and their dual regulatory roles in metastasis (pro-metastatic and anti-metastatic), strategies targeting EV biogenesis, cargo loading, or delivery exhibits translational potential in diagnostics and therapeutics. In this review, we summarize recent advances in understanding the role of breast cancer-derived exosomes in mediating metastatic organotropism and discuss the potential clinical applications of targeting exosomes as novel diagnostic and therapeutic strategies for breast cancer. Full article

Cholangiocarcinoma (CCA) is an aggressive tumor that originates from the epithelial cells of the bile duct and has the ability to metastasize to the liver or lymph nodes at an early stage. CCA metastasis represents a complex, multi-stage cascade process. Among these stages, the acquisition of invasiveness by CCA cells is a critical prerequisite for metastatic progression. Elucidating the molecular mechanisms driving CCA cell invasiveness is critical for advancing our knowledge in this field. Emerging evidence highlights the critical role of non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). These molecules orchestrate key processes such as the epithelial–mesenchymal transition (EMT), as well as the migration and invasion of CCA cells. Collectively, these processes ultimately drive tumor progression. This review comprehensively synthesizes the expression, biogenesis, interactions, signaling pathways, and functional mechanisms of ncRNAs in the invasiveness of CCA. Furthermore, the review discusses potential clinical applications of ncRNAs, including their roles as diagnostic tools, therapeutic targets, and prognostic markers. These investigations offer novel insights and evidence for identifying early metastasis in CCA, developing specific therapeutic strategies, and enhancing drug resistance. Full article

Circular RNAs (circRNAs), a class of covalently closed non-coding RNAs, are pivotal regulators of gene expression and contributors to disease pathogenesis. This study elucidated the biogenesis, functional significance, and regulatory network of circRNA_4083, a novel exon-derived circRNA originating from exons 22 and 23 of the MSH3 gene in chicken. Through comprehensive molecular characterization—including Sanger sequencing, RNase R digestion assays, and subcellular localization—we confirmed the robust stability and predominant cytoplasmic localization of circRNA_4083 across diverse chicken tissues. Mechanistic investigations revealed that reverse complementary sequences within flanking intronic regions are indispensable for its circularization, as demonstrated by overexpression plasmids (#1–#4) in DF-1 cells. Functional analyses demonstrated that circRNA_4083 significantly inhibited cell apoptosis and increased cellular viability. Integrative bioinformatics approaches predicted a competing endogenous RNA (ceRNA) network comprising 12 miRNAs and 2132 target genes (FDR < 0.05), with significant enrichment in pathways critical to genomic stability, including non-homologous end joining (NHEJ) and ubiquitin-mediated proteolysis. These findings position circRNA_4083 as a key modulator of cellular viability and genomic integrity, with potential implications for avian leukosis virus-J (ALV-J) pathogenesis and resistance breeding strategies. This work advances our understanding of circRNA-driven regulatory mechanisms in avian species and underscores their relevance in poultry health. Full article

Opioid use induces neurobiological adaptations throughout mesolimbic brain regions, such as the orbitofrontal cortex (OFC), which mediates decision-making and emotional–cognitive regulation. Previously, we showed that a circular RNA (circRNA) species, rno_circGrin2b_011731 (circGrin2b), is upregulated in the OFC of rats following chronic self-administration (SA) of the opioid heroin. circGrin2b is derived from Grin2b, which encodes the regulatory subunit of the glutamate ionotropic NMDA receptor, GluN2B. However, the upstream regulatory mechanisms of circGrin2b biogenesis and the downstream consequences of circGrin2b dysregulation remain unknown. We hypothesized that opioid-induced elevation of circGrin2b is accompanied by regulation of circRNA biogenesis enzymes, and that circGrin2b may sponge microRNAs (miRNAs), as miRNA sponging is a well-described characteristic of circRNAs. To test these hypotheses, we established an in vitro primary cortical cell culture model to examine alterations in circGrin2b expression following exposure to the opioid morphine. We measured mRNA expression of known circRNA splicing factors and observed significant downregulation of Fused in Sarcoma (Fus), a negative regulator of circRNA biogenesis, following 90 min or 24 h of morphine exposure. Downregulation of Fus at 24 h post-morphine was accompanied by upregulation of circGrin2b and downregulation of miR-26b-3p, a predicted miRNA target of circGrin2b. Luciferase reporter assays confirmed interaction of miR-26b-3p with circGrin2b. Finally, we report a significant negative relationship between circGrin2b and miR-26b-3p expression in the OFC of rats following heroin SA. We conclude that regulation of circGrin2b is an opioid-induced neuroadaptation that may impact downstream signaling of miRNA pathways in the frontal cortex. Full article

The epididymis represents a pivotal organ for sperm maturation and male fertility maintenance. During the epididymal journey, sperm cells undergo morphological and molecular changes that need to acquire the morpho-functional skills necessary for successful oocyte fertilization. Not last, a great enrichment of the spermatozoa RNA payload occurs via an epithelium-derived epididymosome transfer. Currently, circular RNAs (circRNAs), a class of non-coding RNAs (ncRNAs), are acquiring a prominent role in the setting of sperm quality parameters. In this regard, they are considered potential targets in several male infertility conditions. Despite their consolidated role, few notions are known regarding the alleged epididymal backsplicing activity. In the current review, we discuss the main aspects of spermatozoa maturation along the epididymis and the circRNA role in the field of male reproduction. We also report the most recent findings on the circRNA biogenesis that occurs in the epididymal duct, providing new fascinating evidence on epididymal-derived circRNAs. Finally, we show preliminary compelling data on epididymal backsplicing by exploiting the experimental mouse model of aging. Collectively, these data evidence a remarkable role of the epididymis in remodeling the circRNA payload and in shaping its profile in maturating spermatozoa. Full article

Circular RNAs (circRNAs) are a class of unique transcripts characterized by a covalently closed loop structure, which differentiates them from conventional linear RNAs. The formation of circRNAs occurs co-transcriptionally and post-transcriptionally through a distinct type of splicing known as back-splicing, which involves the formation of a head-to-tail splice junction between a 5′ splice donor and an upstream 3′ splice acceptor. This process, along with exon skipping, intron retention, cryptic splice site utilization, and lariat-driven intron processing, results in the generation of three main types of circRNAs (exonic, intronic, and exonic–intronic) and their isoforms. The intricate biogenesis of circRNAs is regulated by the interplay of cis-regulatory elements and trans-acting factors, with intronic Alu repeats and RNA-binding proteins playing pivotal roles, at least in the formation of exonic circRNAs. Various hypotheses regarding pathways of circRNA turnover are forwarded, including endonucleolytic cleavage and exonuclease-mediated degradation; however, similarly to the inconclusive nature of circRNA biogenesis, the process of their degradation and the factors involved remain largely unclear. There is a knowledge gap regarding whether these processes are guided by universal pathways or whether each category of circRNAs requires special tools and particular mechanisms for their life cycles. Understanding these factors is pivotal for fully comprehending the biological significance of circRNAs. This review provides an overview of the various pathways involved in the biogenesis and degradation of different types of circRNAs and explores key factors that have beneficial or adverse effects on the formation and stability of these unique transcripts in higher eukaryotes. Full article

Among the long non-coding RNAs that are currently recognized as important regulatory molecules influencing a plethora of processes in eukaryotic cells, circular RNAs (circRNAs) represent a distinct class of RNAs that are predominantly produced by back-splicing of pre-mRNA. The most studied regulatory mechanisms involving circRNAs are acting as miRNA sponges, forming R-loops with genomic DNA, and encoding functional proteins. In addition to circRNAs generated by back-splicing, two types of circRNAs capable of autonomous RNA-RNA replication and systemic transport have been described in plants: viroids, which are infectious RNAs that cause a number of plant diseases, and retrozymes, which are transcripts of retrotransposon genomic loci that are capable of circularization due to ribozymes. Based on a number of common features, viroids and retrozymes are considered to be evolutionarily related. Here, we provide an overview of the biogenesis mechanisms and regulatory functions of non-replicating circRNAs produced by back-splicing and further discuss in detail the currently available data on viroids and retrozymes, focusing on their structural features, replication mechanisms, interaction with cellular components, and transport in plants. In addition, biotechnological approaches involving replication-capable plant circRNAs are discussed, as well as their potential applications in research and agriculture. Full article

RNA metabolism is focused on RNA molecules and encompasses all the crucial processes an RNA molecule may or will undergo throughout its life cycle. It is an essential cellular process that allows all cells to function effectively. The transcriptomic landscape of a cell is shaped by the processes such as RNA biosynthesis, maturation (RNA processing, folding, and modification), intra- and inter-cellular transport, transcriptional and post-transcriptional regulation, modification, catabolic decay, and retrograde signaling, all of which are interconnected and are essential for cellular RNA homeostasis. In eukaryotes, sRNAs, typically 20–31 nucleotides in length, are a class of ncRNAs found to function as nodes in various gene regulatory networks. sRNAs are known to play significant roles in regulating RNA population at the transcriptional, post-transcriptional, and translational levels. Along with sRNAs, such as miRNAs, siRNAs, and piRNAs, new categories of ncRNAs, i.e., lncRNAs and circRNAs, also contribute to RNA metabolism regulation in eukaryotes. In plants, various genetic screens have demonstrated that sRNA biogenesis mutants, as well as RNA metabolism pathway mutants, exhibit similar growth and development defects, misregulated primary and secondary metabolism, as well as impaired stress response. In addition, sRNAs are both the “products” and the “regulators” in broad RNA metabolism networks; gene regulatory networks involving sRNAs form autoregulatory loops that affect the expression of both sRNA and the respective target. This review examines the interconnected aspects of RNA metabolism with sRNA regulatory pathways in plants. It also explores the potential conservation of these pathways across different kingdoms, particularly in plants and animals. Additionally, the review highlights how cellular RNA homeostasis directly impacts adaptive responses to environmental changes as well as different developmental aspects in plants. Full article

Circular RNAs (circRNAs) have emerged as promising therapeutic targets due to their unique covalently closed-loop structures and their regulatory roles in gene expression. Despite their potential, challenges in circRNA-based therapies include ensuring stability, tissue specificity, and efficient intracellular delivery. This review explores the implications of circRNAs in cardiovascular diseases (CVDs), providing an overview of their biogenesis, molecular mechanisms, and roles in disease pathology. In addition to discussing molecular features, this review highlights therapeutic advances, including small-molecule drugs targeting circRNAs, synthetic circRNA sponges, and innovations in drug delivery systems that enhance the effectiveness of these therapies. Finally, current challenges and future directions are addressed, emphasizing the need for continued research to fully unlock the therapeutic potential of circRNA-based strategies in cardiovascular medicine. Full article

Circular RNAs (circRNAs) are a novel class of noncoding RNAs that have emerged as pivotal players in gene regulation. Our understanding of circRNAs has greatly expanded over the last decade, with studies elucidating their biology and exploring their therapeutic applications. In this review, we provide an overview of the current understanding of circRNA biogenesis, outline their mechanisms of action in cancer, and assess their clinical potential as biomarkers. Furthermore, we discuss circRNAs as a potential therapeutic strategy, including recent advances in circRNA production and translation, along with proof-of-concept preclinical studies of cancer vaccines. Full article

Circular RNA (circRNA) is a type of single-stranded RNA that forms a covalently closed continuous loop, unlike linear RNA. The expression of circRNAs in mammals is often conserved across species and shows tissue and cell specificity. Some circRNA serve as gene regulators. However, the biological function of most circRNAs is unclear. CircRNA does not have 5′ or 3′ ends. The unique structure of circRNAs provides them with a much longer half-life and more resistance to RNase R than linear RNAs. Inflammatory lung responses occur in the pathogenesis and recovery of many lung diseases. Macrophages form the first line of host defense/innate immune responses and initiate/mediate lung inflammation. For example, in bacterial pneumonia, upon pro-inflammatory activation, they release early response cytokines/chemokines that recruit neutrophils, macrophages, and lymphocytes to sites of infection and clear pathogens. The functional effects and mechanisms by which circRNAs exert physiological or pathological roles in macrophage activation and lung inflammation remain poorly understood. In this article, we will review the current understanding and progress of circRNA biogenesis, regulation, secretion, and degradation. Furthermore, we will review the current reports on the role of circRNAs in macrophage activation and polarization, as well as in the process of inflammatory lung responses. Full article

Cardiovascular diseases pose a significant public health challenge globally, necessitating the development of effective treatments to mitigate the risk of cardiovascular diseases. Recently, circular RNAs (circRNAs), a novel class of non-coding RNAs, have been recognized for their role in cardiovascular disease. Aberrant expression of circRNAs is closely linked with changes in various cellular and pathophysiological processes within the cardiovascular system, including metabolism, proliferation, stress response, and cell death. Functionally, circRNAs serve multiple roles, such as acting as a microRNA sponge, providing scaffolds for proteins, and participating in protein translation. Owing to their unique properties, circRNAs may represent a promising biomarker for predicting disease progression and a potential target for cardiovascular drug development. This review comprehensively examines the properties, biogenesis, and potential mechanisms of circRNAs, enhancing understanding of their role in the pathophysiological processes impacting cardiovascular disease. Furthermore, the prospective clinical applications of circRNAs in the diagnosis, prognosis, and treatment of cardiovascular disease are addressed. Full article

Circular RNAs (circRNAs) are cardinal players in numerous physiological and pathological processes. CircRNAs play dual roles as tumor suppressors and oncogenes in different oncological contexts, including hepatocellular carcinoma (HCC). Their roles significantly impact the disease at all stages, including initiation, development, progression, invasion, and metastasis, in addition to the response to treatment. In this review, we discuss the biogenesis and regulatory functional roles of circRNAs, as well as circRNA–protein–mRNA ternary complex formation, elucidating the intricate pathways tuned by circRNAs to modulate gene expression and cellular processes through a comprehensive literature search, in silico search, and bioinformatics analysis. With a particular focus on the interplay between circRNAs, epigenetics, and HCC pathology, the article sets the stage for further exploration of circRNAs as novel investigational theranostic agents in the dynamic realm of HCC. Full article