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Metformin, a widely used oral hypoglycemic drug, has emerged as a potential therapeutic agent for cancer treatment. While initially known for its role in managing diabetes, accumulating evidence suggests that metformin exhibits anticancer properties through various mechanisms. Several cellular or animal experiments have attempted to elucidate the role of non-coding RNA molecules, including microRNAs and long non-coding RNAs, in mediating the anticancer effects of metformin. The present review summarized the current understanding of the mechanisms by which non-coding RNAs modulate the response to metformin in cancer cells. The regulatory roles of non-coding RNAs, particularly miRNAs, in key cellular processes such as cell proliferation, cell death, angiogenesis, metabolism and epigenetics, and how metformin affects these processes are discussed. This review also highlights the role of lncRNAs in cancer types such as lung adenocarcinoma, breast cancer, and renal cancer, and points out the need for further exploration of the mechanisms by which metformin regulates lncRNAs. In addition, the present review explores the potential advantages of metformin-based therapies over direct delivery of ncRNAs, and this review highlights the mechanisms of non-coding RNA regulation when metformin is combined with other therapies. Overall, the present review provides insights into the molecular mechanisms underlying the anticancer effects of metformin mediated by non-coding RNAs, offering novel opportunities for the development of personalized treatment strategies in cancer patients. [ABSTRACT FROM AUTHOR]

ABSTRACT Biosynthesis of specific secondary metabolites in plants involves fine regulation of gene expression. Camellia chekiangoleosa has important economic value: the seeds contain high‐quality unsaturated fatty acids and the pericarp is rich in tea saponins. As an important posttranscriptional regulator, the role of microRNAs (miRNAs) in controlling secondary metabolism in C. chekiangoleosa is not fully studied. Here, we investigated the role of miRNAs and their targets in the secondary metabolic regulatory network by comprehensively analyzing small RNAs, transcriptomes, and degradomes from different tissues. We identified 168 known miRNAs and 74 novel miRNAs in the C. chekiangoleosa genome and revealed 15 tandem clusters containing 35 miRNAs. By establishing a gene regulatory network containing miRNAs, target genes, and transcription factors, we unravelled the multiplicity of miRNA tissue‐specific regulation of gene expression, which may be tightly linked to the synthesis of secondary metabolites. Furthermore, we characterized a novel long‐noncoding miRNA gene (cch‐miR3633) that targeted a UDP‐transferase gene (CchUGT94E5). We showed that, ectopic expression of CchUGT94E5 caused outgrowth of shoot branching and changes in cytokinin contents in Arabidopsis, indicating a potential role of regulating secondary metabolism. This work provides valuable information for the study of miRNA regulation of secondary metabolism. [ABSTRACT FROM AUTHOR]

High‐throughput sequencing has sparked increased research interest in RNA modifications, particularly tRNA methylation, and its connection to various diseases. However, the precise mechanisms underpinning the development of these diseases remain largely elusive. This review sheds light on the roles of several tRNA methylations (m1A, m3C, m5C, m1G, m2G, m7G, m5U, and Nm) in diverse biological functions, including metabolic processing, stability, protein interactions, and mitochondrial activities. It further outlines diseases linked to aberrant tRNA modifications, related enzymes, and potential underlying mechanisms. Moreover, disruptions in tRNA regulation and abnormalities in tRNA‐derived small RNAs (tsRNAs) contribute to disease pathogenesis, highlighting their potential as biomarkers for disease diagnosis. The review also delves into the exploration of drugs development targeting tRNA methylation enzymes, emphasizing the therapeutic prospects of modulating these processes. Continued research is imperative for a comprehensive comprehension and integration of these molecular mechanisms in disease diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Circular (circ) RNAs are non-coding RNAs with important functions in the nervous system, cardiovascular system, and cancer. Their role in atherosclerosis and myocardial infarction (MI) remains poorly described. We aim to investigate the potential circRNAs in immune cells during atherogenesis and examine the most regulated during MI and the modulation by interleukin (IL)-6 receptor inhibition by tocilizumab. Wild-type (WT) and ApoE−/− mice were fed an atherogenic diet for 10 weeks, and the circRNA profile was analyzed by circRNA microarray. Whole blood from patients with ST-elevated MI (STEMI) and randomized to tocilizumab (n = 21) or placebo (n = 19) was collected at admission, 3–7 days, and at 6 months, in addition to samples from healthy controls (n = 13). Primers for human circRNA were designed, and circRNA levels were measured using RT-qPCR. mRNA regulation of predicted circRNA targets was investigated by RNA sequencing. The expression of 867 circRNAs differed between atherogenic and WT mice. In STEMI patients, circUBAC2 was significantly lower than in healthy controls. CircANKRD42 and circUBAC2 levels were inversely correlated with troponin T, and for circUBAC2, an inverse correlation was also seen with final infarct size at 6 months. The predicted mRNA targets for circUBAC2 and circANKRD42 were investigated and altered levels of transcripts involved in the regulation of inflammatory/immune cells, apoptosis, and mitochondrial function were found. Finally, tocilizumab induced an up-regulation of circANKRD42 and circUBAC2 3–7 days after percutaneous coronary intervention. CircRNA levels were dysregulated in STEMI, potentially influencing the immune system, apoptosis, and mitochondrial function. [ABSTRACT FROM AUTHOR]

Epileptogenesis is the process by which a normal brain becomes hyperexcitable and capable of generating spontaneous recurrent seizures. The extensive dysregulation of gene expression associated with epileptogenesis is shaped, in part, by microRNAs (miRNAs) – short, non-coding RNAs that negatively regulate protein levels. Functional miRNA-mediated regulation can, however, be difficult to elucidate due to the complexity of miRNA-mRNA interactions. Here, we integrated miRNA and mRNA expression profiles sampled over multiple time-points during and after epileptogenesis in rats, and applied bi-clustering and Bayesian modelling to construct temporal miRNA-mRNA-mRNA interaction networks. Network analysis and enrichment of network inference with sequence- and human disease-specific information identified key regulatory miRNAs with the strongest influence on the mRNA landscape, and miRNA-mRNA interactions closely associated with epileptogenesis and subsequent epilepsy. Our findings underscore the complexity of miRNA-mRNA regulation, can be used to prioritise miRNA targets in specific systems, and offer insights into key regulatory processes in epileptogenesis with therapeutic potential for further investigation. [ABSTRACT FROM AUTHOR]

Motivation The advent of multimodal omics data has provided an unprecedented opportunity to systematically investigate underlying biological mechanisms from distinct yet complementary angles. However, the joint analysis of multi-omics data remains challenging because it requires modeling interactions between multiple sets of high-throughput variables. Furthermore, these interaction patterns may vary across different clinical groups, reflecting disease-related biological processes. Results We propose a novel approach called Differential Canonical Correlation Analysis (dCCA) to capture differential covariation patterns between two multivariate vectors across clinical groups. Unlike classical Canonical Correlation Analysis, which maximizes the correlation between two multivariate vectors, dCCA aims to maximally recover differentially expressed multivariate-to-multivariate covariation patterns between groups. We have developed computational algorithms and a toolkit to sparsely select paired subsets of variables from two sets of multivariate variables while maximizing the differential covariation. Extensive simulation analyses demonstrate the superior performance of dCCA in selecting variables of interest and recovering differential correlations. We applied dCCA to the Pan-Kidney cohort from the Cancer Genome Atlas Program database and identified differentially expressed covariations between noncoding RNAs and gene expressions. Availability and Implementation The R package that implements dCCA is available at https://github.com/hwiyoungstat/dCCA. [ABSTRACT FROM AUTHOR]

The dysfunction of several types of regulators, including miRNAs, has recently attracted scientific attention for their role in cancer-associated changes in gene expression. MiRNAs are small RNAs of ~22 nt in length that do not encode protein information but play an important role in post-transcriptional mRNA regulation. Studies have shown that miRNAs are involved in tumour progression, including cell proliferation, cell cycle, apoptosis, and tumour angiogenesis and invasion, and play a complex and important role in the regulation of tumourigenesis. The detection of selected miRNAs may help in the early detection of cancer cells, and monitoring changes in their expression profile may serve as a prognostic factor in the course of the disease or its treatment. MiRNAs may serve as diagnostic and prognostic biomarkers, as well as potential therapeutic targets for colorectal cancer. In recent years, there has been increasing evidence for an epigenetic interaction between DNA methylation and miRNA expression in tumours. This article provides an overview of selected miRNAs, which are more frequently expressed in colorectal cancer cells, suggesting an oncogenic nature. [ABSTRACT FROM AUTHOR]

Some years ago, we reported the generation of a Fanconi anemia (FA) microRNA signature. This study aims to develop an analytical strategy to select a smaller and more reliable set of molecules that could be tested for potential benefits for the FA phenotype, elucidate its biochemical and molecular mechanisms, address experimental activity, and evaluate its possible impact on FA therapy. In silico analyses of the data obtained in the original study were thoroughly processed and anenrichment analysis was employed to identify the classes of genes that are over-represented in the FA-miRNA population under study. Primary bone marrow mononuclear cells (MNCs) from sixFA patients and sixhealthy donors as control samples were employed in the study. RNAs containing the small RNA fractions were reverse-transcribed and real-time PCR was performed in triplicate using the specific primers. Experiments were performed in triplicate.The in-silico analysis reported six miRNAs as likely contributors to the complex pathological spectrum of FA. Among these, three miRNAs were validated by real-time PCR. Primary bone marrow mononuclear cells (MNCs) reported a significant reduction in the expression level of miRNA-1246 and miRNA-206 in the FA samples in comparison to controls.This study highlights several biochemical pathways as culprits in the phenotypic manifestations and the pathophysiological mechanisms acting in FA. A relatively low number of miRNAs appear involved in all these different phenotypes, demonstrating the extreme plasticity of the gene expression modulation. This study further highlights miR-206 as a pivotal player in regulatory functions and signaling in the bone marrow mesenchymal stem cell (BMSC) process in FA. Due to this evidence, the activity of miR-206 in FA deserves specific experimental scrutiny. The results, here presented, might be relevant in the management of FA. [ABSTRACT FROM AUTHOR]

Background: RNA methyltransferase-like 3 (METTL3) is responsible for methyl group transfer in the progression of N6-methyladenosine (m6A) modification. This epigenetic feature contributes to the structural and functional regulation of RNA and consequently may promote tumorigenesis, tumor progression, and cellular response to anticancer treatment (chemo-, radio-, and immunotherapy). In head and neck squamous cell carcinoma (HNSCC), the commonly used chemotherapy is cisplatin. Unfortunately, cisplatin resistance is still a major cause of tumor relapse and patients' death. Thus, this study aimed to investigate the role of METTL3 on cellular response to cisplatin in HNSCC in vitro models Materials and methods: HNSCC cell lines (H103, FaDu, and Detroit-562) with stable METTL3 knockdown (sgMETTL3) established with CRISPR-Cas9 system were treated with 0.5 tolerable plasma level (TPL) and 1 TPL of cisplatin. Further, cell cycle distribution, apoptosis, CD44/CD133 surface marker expression, and cell's ability to colony formation were analyzed in comparison to controls (cells transduced with control sgRNA). Results: The analyses of cell cycle distribution and apoptosis indicated a significantly higher percentage of cells with METTL3 knockdown 1) arrested in the G2/S phase and 2) characterized as a late apoptotic or death in comparison to control. The colony formation assay showed intensified inhibition of a single cell's ability to grow into a colony in FaDu and Detroit-562 METTL3-deficient cells, while a higher colony number was observed in H103 METTL3 knockdown cells after cisplatin treatment. Also, METTL3 deficiency significantly increased cancer stem cell markers' surface expression in all studied cell lines. Conclusion: Our findings highlight the significant influence of METTL3 on the cellular response to cisplatin, suggesting its potential as a promising therapeutic target for addressing cisplatin resistance in certain cases of HNSCC. [ABSTRACT FROM AUTHOR]

In recent years, seminal studies have been devoted to unraveling the puzzling mysteries associated with the cancer preventive/inhibitory role of melatonin. Our current knowledge of the translational mechanisms and the detailed structural insights have highlighted the characteristically exclusive role of melatonin in the inhibition of carcinogenesis and metastatic dissemination. This mini‐review outlines recent discoveries related to mechanistic role of melatonin in prevention of carcinogenesis and metastasis. Moreover, another exciting facet of this mini‐review is related to phenomenal breakthroughs linked with regulation of noncoding RNAs by melatonin in wide variety of cancers. Significance statement: There has been a paradigm shift in our understanding related to metamorphosis of simplistic view about melatonin from a sleep inducer to mechanistic role of melatonin in cancer prevention. Furthermore, regulation of noncoding RNAs particularly long noncoding RNAs and circular RNAs is adding another layer of complexity. [ABSTRACT FROM AUTHOR]

The exosome multiprotein complex plays a critical role in RNA processing and degradation. This system governs the regulation of mRNA quality, degradation in the cytoplasm, the processing of short noncoding RNA, and the breakdown of RNA fragments. We determined two crystal structures of exosome components from Thermoplasma acidophilum (Taci): one with a resolution of 2.3 Å that reveals the central components (TaciRrp41 and TaciRrp42), and another with a resolution of 3.5 Å that displays the whole exosome (TaciRrp41, TaciRrp42, and TaciRrp4). The fundamental exosome structure revealed the presence of a heterodimeric complex consisting of TaciRrp41 and TaciRrp42. The structure comprises nine subunits, with TaciRrp41 and TaciRrp42 arranged in a circular configuration, while TaciRrp4 is located at the apex. The RNA degradation capabilities of the TaciRrp4:41:42 complex were verified by RNA degradation assays, consistent with prior findings in other archaeal exosomes. The resemblance between archaeal exosomes and bacterial PNPase suggests a common mechanism for RNA degradation. Despite sharing comparable topologies, the surface charge distributions of TaciRrp4 and other archaea structures are surprisingly distinct. Different RNA breakdown substrates may be responsible for this variation. These newfound structural findings enhance our comprehension of RNA processing and degradation in biological systems. [ABSTRACT FROM AUTHOR]

Myocardial cell fate specification takes place during the early stages of heart development as the precardiac mesoderm is configured into two symmetrical sets of bilateral precursor cells. Molecular cues of the surrounding tissues specify and subsequently determine the early cardiomyocytes, that finally matured as the heart is completed at early postnatal stages. Over the last decade, we have greatly enhanced our understanding of the transcriptional regulation of cardiac development and thus of myocardial cell fate. The recent discovery of a novel layer of gene regulation by non-coding RNAs has flourished their implication in epigenetic, transcriptional and post-transcriptional regulation of cardiac development. In this review, we revised the current state-of-the-art knowledge on the functional role of non-coding RNAs during myocardial cell fate. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are small RNA molecules that regulate more than 30% of genes in humans. Recent studies have revealed that miRNAs play a crucial role in tumorigenesis. Large sets of miRNAs in human tumors are under-expressed compared to normal tissues. Furthermore, experiments have shown that interference with miRNA processing enhances tumorigenesis. Multiple studies have documented the causal role of miRNAs in cancer, and miRNA-based anticancer therapies are currently being developed. This review primarily focuses on two key points: (1) miRNAs and their role in human cancer and (2) the regulation of tumor suppressors by miRNAs. The review discusses (a) the regulation of the tumor suppressor p53 by miRNA, (b) the critical role of the miR-144/451 cluster in regulating the Itch-p63-Ago2 pathway, and (c) the regulation of PTEN by miRNAs. Future research and the perspectives of miRNA in cancer are also discussed. Understanding these pathways will open avenues for therapeutic interventions targeting miRNA regulation. [ABSTRACT FROM AUTHOR]

Transforming growth factor (TGF-β) plays a dual role in tumor progression as well as a pivotal role in radiation response. TGF-β-related epigenetic regulations, including DNA methylation, histone modifications (including methylation, acetylation, phosphorylation, ubiquitination), chromatin remodeling and non-coding RNA regulation, have been found to affect the occurrence and development of tumors as well as their radiation response in multiple dimensions. Due to the significance of radiotherapy in tumor treatment and the essential roles of TGF-β signaling in radiation response, it is important to better understand the role of epigenetic regulation mechanisms mediated by TGF-β signaling pathways in radiation-induced targeted and non-targeted effects. By revealing the epigenetic mechanism related to TGF-β-mediated radiation response, summarizing the existing relevant adjuvant strategies for radiotherapy based on TGF-β signaling, and discovering potential therapeutic targets, we hope to provide a new perspective for improving clinical treatment. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a type of intestinal cancer that causes more than 600,000 deaths every year. Overcoming the problems of metastasis requires detailed studies to reveal the potential molecular mechanisms. This study aims to reveal the molecular mechanism of CRC metastasis involving non-coding RNA regulation. The expression profile of FTH1P3 was analyzed based on the data of TCGA-COAD patient cohorts. Q-PCR analysis was performed to validate the expression of FTH1P3 in colorectal cancer cells. JASPR was used to screen transcription factors of FTH1P3. q-ChIP analysis was used to validate the target between FTH1P3 and transcription factor. Scratch assay and transwell assay were used to evaluate the migration and invasion ability of colorectal cancer cells. FTH1P3 is highly expressed in CRC patient cohort. FTH1P3 induced migration and invasion of SW480 cell through regulating epithelial-mesenchymal transition (EMT). In addition, FTH1P3 is a direct target of SNAI2. SNAI2 promotes the expression of FTH1P3. Both FTH1P3 and SNAI2 were directly targeted and repressed by miR-218-5p. Interestingly, ectopic FTH1P3 caused a decreased miR-218-5p level and an elevated nucleic SNAI2 protein expression level. Of note, only ectopic SNAI2 protein resulted in a repressed miR-218-5p and an increased FTH1P3, whereas SNAI2 3'UTR failed to affect the expression of miR-218-5p and FTH1P3. SNAI2 transcriptionally activates FTH1P3 expression. Both SNAI2 and FTH1P3 are targets of miR-218-5p. SNAI2/FTH1P3/miR-218-5p form a positive feedback loop in the regulation of CRC metastasis. [ABSTRACT FROM AUTHOR]

Aortic aneurysms (AA) and aorta dissection (AD) are life-threatening conditions with a rising incidence and high mortality rate. Recent research has linked non-coding RNAs to the regulation of AA and AD progression. In this study, we performed circRNA sequencing, microRNA (miRNA) sequencing, and messenger RNA (mRNA) sequencing on plasma samples from AA and AD patients to identify the key circRNA-miRNA-mRNA axis involved in the transition from AA to AD. Our results showed elevated levels of circ_0000006 and circ_0000160, along with decreased levels of hsa-let-7e-5p in AD samples compared to AA samples. Predictive analysis suggested that circ_0000006 and circ_0000160 potentially target hsa-let-7e-5p, which in turn may bind to the mRNA of Ubiquilin 4 (UBQLN4). In an AD cell model using vascular smooth muscle cells (VSMCs), silencing circ_0000006 and circ_0000160 attenuated the effects of platelet-derived growth factor (PDGF)-induced phenotypic changes, proliferation, and migration. This effect was partially reversed by inhibiting hsa-let-7e-5p. Furthermore, we found that overexpression of UBQLN4 counteracted the effects of hsa-let-7e-5p, suggesting UBQLN4 as a downstream mediator of hsa-let-7e-5p. In an animal model of AD, knockdown of circ_0000006 and circ_0000160 also showed protective effects against aortic septation. Overall, our findings indicate that the upregulation of circ_0000006 and circ_0000160 contributes to the progression from AA to AD by influencing abnormal phenotypic changes, migration, and proliferation of VSMCs. The Hsa-let-7e-5p/UBQLN4 axis may play a critical role in AD development. Targeting circ_0000006 and circ_0000160 could be a potential therapeutic strategy for preventing the progression of AD. [ABSTRACT FROM AUTHOR]

Background: IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis in the world, but the disease pathogenesis noncoding is yet to be elucidated. Previous studies have revealed regulatory functions for long noncoding RNA (lncRNA) in various diseases; however, the roles of lncRNA in IgAN and regulation of transcription factors (TFs) have been scarcely investigated. Methods: Renal tissue samples (n = 5) from patients with IgAN and control samples (n = 4) were collected and RNA sequencing (RNA-seq) was performed. Four software programs were employed for lncRNA prediction. GO (Gene Ontology)/KEGG (Kyoto Encyclopedia of Genes and Genomes) were employed for analysis of the identified differentially expressed genes (DEGs). A regulatory network model of DE lncRNA-TF-DEG was developed, and the levels of expression of key lncRNAs, TFs, and corresponding target genes were assessed using qRT-PCR and immunofluorescence. Results: The current study identified 674 upregulated and 1,011 downregulated DE mRNAs and 260 upregulated and 232 downregulated DE lncRNAs in IgAN samples compared with control samples. The upregulated DE mRNAs showed enrichment in cell adhesion and collagen glial fiber organization pathways. The DE lncRNAs-DE mRNAs showing co-expression are associated with transmembrane transport. A novel regulatory network model of lncRNA-TF-DEG has been developed. This study identified seven TFs that are cis-regulated by 6 DE lncRNAs, and show co-expression with 132 DEGs (correlation coefficient ≥ 0.8, P ≤ 0.01), generating 158 pairs that showed co-expression. The lncRNAs NQO1-DT and RP5-1057120.6 were found to be highly expressed in IgAN samples. The TFs vitamin D Receptor (VDR) and NFAT5, along with their target genes were also aberrantly expressed. Conclusion: Key lncRNAs and TFs centrally associated with IgAN have been identified in this study. A regulatory network model of lncRNA-TF-mRNA was constructed. Further studies on the genes identified herewith could provide insight into the pathogenesis of IgAN. [ABSTRACT FROM AUTHOR]

A major mechanism of post-transcriptional RNA regulation in cells is the addition of chemical modifications to RNA nucleosides, which contributes to nearly every aspect of the RNA life cycle. N6-methyladenosine (m6A) is a highly prevalent modification in cellular mRNAs and non-coding RNAs, and it plays important roles in the control of gene expression and cellular function. Within the brain, proper regulation of m6A is critical for neurodevelopment, learning and memory, and the response to injury, and m6A dysregulation has been implicated in a variety of neurological disorders. Thus, understanding m6A and how it is regulated in the brain is important for uncovering its roles in brain function and potentially identifying novel therapeutic pathways for human disease. Much of our knowledge of m6A has been driven by technical advances in the ability to map and quantify m6A sites. Here, we review current technologies for characterizing m6A and highlight emerging methods. We discuss the advantages and limitations of current tools as well as major challenges going forward, and we provide our perspective on how continued developments in this area can propel our understanding of m6A in the brain and its role in brain disease. [ABSTRACT FROM AUTHOR]

Lymphomas, complex and heterogeneous malignant tumors, originate from the lymphopoietic system. These tumors are notorious for their high recurrence rates and resistance to treatment, which leads to poor prognoses. As ongoing research has shown, epigenetic modifications like DNA methylation, histone modifications, non-coding RNA regulation, and RNA modifications play crucial roles in lymphoma pathogenesis. Epigenetic modification–targeting drugs have exhibited therapeutic efficacy and tolerability in both monotherapy and combination lymphoma therapy. This review discusses pathogenic mechanisms and potential epigenetic therapeutic targets in common lymphomas, offering new avenues for lymphoma diagnosis and treatment. We also discuss the shortcomings of current lymphoma treatments, while suggesting potential areas for future research, in order to improve the prediction and prognosis of lymphoma. [ABSTRACT FROM AUTHOR]

Post-transcriptional regulation by small RNAs and post-translational modifications (PTM) such as lysine acetylation play fundamental roles in physiological circuits, offering rapid responses to environmental signals with low energy consumption. Yet, the interplay between these regulatory systems remains underexplored. Here, we unveil the cross-talk between sRNAs and lysine acetylation in Streptococcus mutans, a primary cariogenic pathogen known for its potent acidogenic virulence. Through systematic overexpression of sRNAs in S. mutans, we identified sRNA SmsR1 as a critical player in modulating acidogenicity, a key cariogenic virulence feature in S. mutans. Furthermore, combined with the analysis of predicted target mRNA and transcriptome results, potential target genes were identified and experimentally verified. A direct interaction between SmsR1 and 5'-UTR region of pdhC gene was determined by in vitro binding assays. Importantly, we found that overexpression of SmsR1 reduced the expression of pdhC mRNA and increased the intracellular concentration of acetyl-CoA, resulting in global changes in protein acetylation levels. This was verified by acetyl-proteomics in S. mutans, along with an increase in acetylation level and decreased activity of LDH. Our study unravels a novel regulatory paradigm where sRNA bridges post-transcriptional regulation with post-translational modification, underscoring bacterial adeptness in fine-tuning responses to environmental stress. Author summary: Post-transcriptional regulation and post-translational modification are widely present in physiological circuits due to their low energy consumption and rapid response to the environment. sRNA is an important post-transcriptional regulatory factor in bacterial response to environmental stress, and bacteria also use sRNA as a key signal to control multicellular behaviors such as biofilm formation and quorum sensing to regulate virulence. S. mutans is an intractable cariogenic pathogen, but the role of sRNA in S. mutans is poorly understood. Here, we elucidated the virulence regulation and mechanism of sRNA SmsR1 in S. mutans by means of transcriptomics, acetyl-proteomics and animal models, and found its relationship with protein acetylation (post-translational modification), and a new role of sRNA physiological regulatory network was shown. This study presents an innovative perspective that a sRNA in S. mutans is involved in the correlation between post-transcriptional regulation and post-translational modification. [ABSTRACT FROM AUTHOR]

Argonaute proteins, guided by small RNAs, play crucial roles in gene regulation and genome protection through RNA interference (RNAi)-related mechanisms. Ribosomal RNAs (rRNAs), encoded by repeated rDNA units, constitute the core of the ribosome being the most abundant cellular transcripts. rDNA clusters also serve as sources of small RNAs, which are loaded into Argonaute proteins and are able to regulate rDNA itself or affect other gene targets. In this review, we consider the impact of small RNA pathways, specifically siRNAs and piRNAs, on rRNA gene regulation. Data from diverse eukaryotic organisms suggest the potential involvement of small RNAs in various molecular processes related to the rDNA transcription and rRNA fate. Endogenous siRNAs are integral to the chromatin-based silencing of rDNA loci in plants and have been shown to repress rDNA transcription in animals. Small RNAs also play a role in maintaining the integrity of rDNA clusters and may function in the cellular response to rDNA damage. Studies on the impact of RNAi and small RNAs on rRNA provide vast opportunities for future exploration. [ABSTRACT FROM AUTHOR]

Abstract—RNA polymerase III synthesizes a wide range of noncoding RNAs shorter than 400 nucleotides in length. These RNAs are involved in protein synthesis (tRNA, 5S rRNA, and 7SL RNA), maturation, and splicing of different types of RNA (RPR, MRP RNA, and U6 snRNA), regulation of transcription (7SK RNA), replication (Y RNA), and intracellular transport (vault RNA). BC200 and BC1 RNA genes are transcribed by RNA polymerase III in neurons only where these RNAs regulate protein synthesis. Mutations in the regulatory elements of the genes transcribed by RNA polymerase III as well as in transcription factors of this RNA polymerase are associated with the development of a number of diseases, primarily oncological and neurological. In this regard, the mechanisms of regulation of the expression of the genes containing various RNA polymerase III promoters were actively studied. This review describes the structural and functional classification of polymerase III promoters, as well as the factors involved in the regulation of promoters of different types. A number of examples demonstrate the role of the described factors in the pathogenesis of human diseases. [ABSTRACT FROM AUTHOR]

Diabetic cardiomyopathy (DCM) is a major factor in the development of heart failure. Mitochondria play a crucial role in regulating insulin resistance, oxidative stress, and inflammation, which affect the progression of DCM. Regular exercise can induce altered non-coding RNA (ncRNA) expression, which subsequently affects gene expression and protein function. The mechanism of exercise-induced mitochondrial-related non-coding RNA network in the regulation of DCM remains unclear. This study seeks to construct an innovative exercise-induced mitochondrial-related ncRNA network. Bioinformatic analysis of RNA sequencing data from an exercise rat model identified 144 differentially expressed long non-coding RNA (lncRNA) with cutoff criteria of p< 0.05 and fold change ≥1.0. GSE6880 and GSE4745 were the differentially expressed mRNAs from the left ventricle of DCM rat that downloaded from the GEO database. Combined with the differentially expressed mRNA and MitoCarta 3.0 dataset, the mitochondrial located gene Pdk4 was identified as a target gene. The miRNA prediction analysis using miRanda and TargetScan confirmed that 5 miRNAs have potential to interact with the 144 lncRNA. The novel lncRNA-miRNA-Pdk4 network was constructed for the first time. According to the functional protein association network, the newly created exercise-induced ncRNA network may serve as a promising diagnostic marker and therapeutic target, providing a fresh perspective to understand the molecular mechanism of different exercise types for the prevention and treatment of diabetic cardiomyopathy. [ABSTRACT FROM AUTHOR]

Malignant tumor cells go through morphological and gene expression alterations, including rearrangement of cytoskeleton proteins that promote invasion and metastasis. Microtubules form a major cytoskeleton component that plays a significant role in regulating multiple cellular activities and function depending on the presence of posttranslational modification (PTM). Acetylation is a type of PTM that generally occurs in the lysine 40 region of α‐tubulin and is known to be critically associated with cancer metastasis. Current evidence demonstrates that noncoding RNAs, such as long noncoding RNA (lncRNA) and microRNA (or miRNA), which are correlated with gene regulation modulate the expression of acetylated tubulin in the development and metastasis of cancer. This review provides an overview about the role of lncRNA and miRNA in regulation of tubulin acetylation in various types of cancer. Significance statement: Tubulin acetylation is one of the primary factors contributing to cancer progression and metastasis. It is commonly observed in various cancers like breast cancer, lung cancer, nasopharyngeal carcinoma, and pancreatic cancer. Through the different courses of cancer development, lncRNA and microRNA regulate the expression of this tubulin acetylation. In spite of a number of research studies reporting relationships of various lncRNAs and microRNAs with Tubulin acetylation, a comprehensive review highlighting their interrelationship has yet not been discussed. Understanding their association in depth will be beneficial in developing new treatments for cancer patients. [ABSTRACT FROM AUTHOR]

High night temperature stress is one of the main environmental factors affecting rice yield and quality. More and more evidence shows that microRNA (miRNA) plays an important role in various abiotic stresses. However, the molecular network of miRNA regulation on rice tolerance to high night temperatures remains unclear. Here, small RNA, transcriptome and degradome sequencing were integrated to identify differentially expressed miRNAs, genes, and key miRNA-target gene pairs in rice heat-sensitive and heat-tolerant lines at the filling stage suffering from high night temperature stress. It was discovered that there were notable differences in the relative expression of 102 miRNAs between the two rice lines under stress. Meanwhile, 5263 and 5405 mRNAs were differentially expressed in the heat-sensitive line and heat-tolerant line, and functional enrichment analysis revealed that these genes were involved in heatrelated processes and pathways. The miRNAs-mRNAs target relationship was further verified by degradome sequencing. Eventually, 49 miRNAs-222 mRNAs target pairs with reverse expression patterns showed significant relative expression changes between the heat-tolerant and the heat-sensitive line, being suggested to be responsible for the heat tolerance difference of these two rice lines. Functional analysis of these 222 mRNA transcripts showed that high night temperature-responsive miRNAs targeted these mRNAs involved in many heat-related biological processes, such as transcription regulation, chloroplast regulation, mitochondrion regulation, protein folding, hormone regulation and redox process. This study identified possible miRNA-mRNA regulation relationships in response to high night temperature stress in rice and potentially contributed to heat resistance breeding of rice in the future. [ABSTRACT FROM AUTHOR]

The concept of competitive endogenous RNA regulation has brought on a change in the way we think about transcriptional regulation by miRNA–mRNA interactions. Rather than the relatively simple idea of miRNAs negatively regulating mRNA transcripts, mRNAs and other non-coding RNAs can regulate miRNAs and, therefore, broad networks of gene products through competitive interactions. While this concept is not new, its significant roles in and implications on cancer have just recently come to light. The field is now ripe for the extrapolation of technologies with a substantial clinical impact on cancer. With the majority of the genome consisting of non-coding regions encoding regulatory RNAs, genomic alterations in cancer have considerable effects on these networks that have been previously unappreciated. Triple-negative breast cancer (TNBC) is characterized by high mutational burden, genomic instability and heterogeneity, making this aggressive breast cancer subtype particularly relevant to these changes. In the past few years, much has been learned about the roles of competitive endogenous RNA network regulation in tumorigenesis, disease progression and drug response in triple-negative breast cancer. In this review, we present a comprehensive view of the new knowledge and future perspectives on competitive endogenous RNA networks affected by genomic alterations in triple-negative breast cancer. An overview of the competitive endogenous RNA (ceRNA) hypothesis and its bearing on cellular function and disease is provided, followed by a thorough review of the literature surrounding key competitive endogenous RNAs in triple-negative breast cancer, the genomic alterations affecting them, key disease-relevant molecular and functional pathways regulated by them and the clinical implications and significance of their dysregulation. New knowledge of the roles of these regulatory mechanisms and the current acceleration of research in the field promises to generate insights into the diagnosis, classification and treatment of triple-negative breast cancer through the elucidation of new molecular mechanisms, therapeutic targets and biomarkers. [ABSTRACT FROM AUTHOR]

RNA plays an indispensable role in mammalian cell functions. Cas13, a class of RNA-guided ribonuclease, is a flexible tool for modifying and regulating coding and non-coding RNAs, with enormous potential for creating new cell functions. However, the lack of control over Cas13 activity has limited its cell engineering capability. Here, we present the CRISTAL (Control of RNA with Inducible SpliT CAs13 Orthologs and Exogenous Ligands) platform. CRISTAL is powered by a collection (10 total) of orthogonal split inducible Cas13 effectors that can be turned ON or OFF via small molecules in multiple cell types, providing precise temporal control. Also, we engineer Cas13 logic circuits that can respond to endogenous signaling and exogenous small molecule inputs. Furthermore, the orthogonality, low leakiness, and high dynamic range of our inducible Cas13d and Cas13b enable the design and construction of a robust incoherent feedforward loop, leading to near-perfect and tunable adaptation response. Finally, using our inducible Cas13 effectors, we achieve simultaneous multiplexed control of multiple genes in vitro and in mice. Together, our CRISTAL design represents a powerful platform for precisely regulating RNA dynamics to advance cell engineering and elucidate RNA biology. The lack of control over Cas13 activity has limited its utility. Here the authors report Control of RNA with Inducible SpliT CAs13 Orthologs and Exogenous Ligands (CRISTAL), controlled by orthogonal split inducible Cas13 effectors that can be turned ON or OFF, providing precise temporal control. [ABSTRACT FROM AUTHOR]

RNA structure folding largely influences RNA regulation by providing flexibility and functional diversity. In silico and in vitro analyses are limited in their ability to capture the intricate relationships between dynamic RNA structure and RNA functional diversity present in the cell. Here, we investigate sequence, structure and functional features of mouse and human SINE-transcribed retrotransposons embedded in SINEUPs long non-coding RNAs, which positively regulate target gene expression post-transcriptionally. In-cell secondary structure probing reveals that functional SINEs-derived RNAs contain conserved short structure motifs essential for SINEUP-induced translation enhancement. We show that SINE RNA structure dynamically changes between the nucleus and cytoplasm and is associated with compartment-specific binding to RBP and related functions. Moreover, RNA–RNA interaction analysis shows that the SINE-derived RNAs interact directly with ribosomal RNAs, suggesting a mechanism of translation regulation. We further predict the architecture of 18 SINE RNAs in three dimensions guided by experimental secondary structure data. Overall, we demonstrate that the conservation of short key features involved in interactions with RBPs and ribosomal RNA drives the convergent function of evolutionarily distant SINE-transcribed RNAs. Here the authors elucidate structure-function relationships of SINEUPs, antisense long non-coding RNAs that through SINE repeat elements positively regulate protein translation of mRNAs they pair with. SINEUP's functional domains do not share common ancestors. [ABSTRACT FROM AUTHOR]

Breast cancer is the major cancer that affects women all over the world. The awareness over past several decades has led to intensive screening and detection as well as successful treatments. Still, the breast cancer mortality is unacceptable and needs to be urgently addressed. Among many factors, inflammation has often been associated with tumorigenesis, including breast cancer. More than a third of all breast cancer deaths are marked by deregulated inflammation. The exact mechanisms are still not completely known but among the many putative factors, the epigenetic changes, particularly those mediated by non-coding RNAs are fascinating. microRNAs, long non-coding RNAs as well as circular RNAs seem to impact the inflammation in breast cancer which further highlights their important regulatory role in breast cancer pathogenesis. Understanding inflammation in breast cancer and its regulation by non-coding RNAs is the primary objective of this review article. We attempt to provide the most complete information on the topic in hopes of opening new areas of research and discoveries. [ABSTRACT FROM AUTHOR]

Simple Summary: The study examines how different prenatal nutrition plans affect muscle development and epigenetic mechanisms in Nellore cows' offspring. It looks at 63 male calves from cows given no supplementation (NP), partial supplementation (PP), or full supplementation (CP) during pregnancy. RNA sequencing showed no difference in epigenetic mechanisms, but did reveal 1823 transcripts at 15 months and 1533 at 22 months. Among these, a few showed differences between groups. Interestingly, while maternal nutrition didn't affect epigenetic mechanisms directly, it seemed to influence how certain RNA molecules regulated them. Maternal nutrition has the ability of influence critical processes in fetal life, including muscle development. Also, in this period, epigenetic sensitivity to external stimuli is higher and produces long-lasting effects. Thus, the aim of this study was to investigate epigenetic mechanisms, including the identification and characterization of long non-coding RNA (lncRNA) from animals that had undergone different strategies of prenatal supplementation. A group of Nellore cows (n = 126) were separated into three nutritional plans: NP (control)—Not Programmed, without protein–energy supplementation; PP—Partially Programmed, protein–energy supplementation in the final third of pregnancy; and CP—Complete Programming, protein–energy supplementation during the full period of gestation. A total of 63 male offspring were used in this study, of which 15 (5 per treatment) had Longissimus thoracis muscle at 15 (biopsy) and 22 months (slaughter). Biopsy samples were subjected to RNA extraction and sequencing. Differential expression (DE) of remodeling factors and chromatin-modifying enzyme genes were performed. For the identification and characterization of lncRNA, a series of size filters and protein coding potential tests were performed. The lncRNAs identified had their differential expression and regulatory potential tested. Regarding DE of epigenetic mechanisms, no differentially expressed gene was found (p > 0.1). Identification of potential lncRNA was successful, identifying 1823 transcripts at 15 months and 1533 at 22 months. Among these, four were considered differentially expressed between treatments at 15 months and 6 were differentially expressed at 22 months. Yet, when testing regulatory potential, 13 lncRNAs were considered key regulators in the PP group, and 17 in the CP group. PP group lncRNAs possibly regulate fat-cell differentiation, in utero embryonic development, and transforming growth factor beta receptor, whereas lncRNA in the CP group regulates in utero embryonic development, fat-cell differentiation and vasculogenesis. Maternal nutrition had no effect on differential expression of epigenetic mechanisms; however, it seems to impair lncRNA regulation of epigenetics. [ABSTRACT FROM AUTHOR]

Recently, myriad studies have defined the versatile abilities of gasotransmitters and their synthesizing enzymes to play a "Maestro" role in orchestrating several oncological and non-oncological circuits and, thus, nominated them as possible therapeutic targets. Although a significant amount of work has been conducted on the role of nitric oxide (NO) and carbon monoxide (CO) and their inter-relationship in the field of oncology, research about hydrogen sulfide (H2S) remains in its infancy. Recently, non-coding RNAs (ncRNAs) have been reported to play a dominating role in the regulation of the endogenous machinery system of H2S in several pathological contexts. A growing list of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are leading the way as upstream regulators for H2S biosynthesis in different mammalian cells during the development and progression of human diseases; therefore, their targeting can be of great therapeutic benefit. In the current review, the authors shed the light onto the biosynthetic pathways of H2S and their regulation by miRNAs and lncRNAs in various oncological and non-oncological disorders. [ABSTRACT FROM AUTHOR]

Skeletal muscle is a critical component of goose meat and a significant economic trait of geese. The regulatory roles of miRNAs and lncRNAs in the maturation stage of goose skeletal muscle are still unclear. Therefore, this study conducted experiments on the leg muscles of Magang geese at two stages: 3-day post-hatch (P3) and 3 months (M3). Morphological observations revealed that from P3 to M3, muscle fibers mainly underwent hypertrophy and maturation. The muscle fibers became thicker, nuclear density decreased, and nuclei moved towards the fiber edges. Additionally, this study analyzed the expression profiles of lncRNAs, miRNAs, and mRNAs during the skeletal muscle fiber maturation stage, identifying 1,949 differentially expressed mRNAs (DEMs), 21 differentially expressed miRNAs (DEMIs), and 172 differentially expressed lncRNAs (DELs). Furthermore, we performed enrichment analyses on DEMs, cis-regulatory genes of DELs, and target DEMs of DEMIs, revealing significant enrichment of signaling pathways including MAPK, PPAR, and mTOR signaling pathways. Among these, the MAPK signaling pathway was the only pathway enriched across all three types of differentially expressed RNAs, indicating its potentially more significant role in skeletal muscle maturation. Finally, this study integrated the targeting relationships between DELs, DEMs, and DEMIs from these two stages to construct a ceRNA regulatory network. These findings unveil the potential functions and mechanisms of lncRNAs and miRNAs in the growth and development of goose skeletal muscle and provide valuable references for further exploration of the mechanism underlying the maturation of Magang geese leg muscle. [ABSTRACT FROM AUTHOR]

Commensal and pathogenic bacteria continuously evolve to survive in diverse ecological niches by efficiently coordinating gene expression levels in their ever-changing environments. Regulation through the RNA transcript itself offers a faster and more cost-effective way to adapt than protein-based mechanisms and can be leveraged for diagnostic or antimicrobial purposes. However, RNA can fold into numerous intricate, not always functional structures that both expand and obscure the plethora of roles that regulatory RNAs serve within the cell. Here, we review the current knowledge of bacterial non-coding RNAs in relation to their folding pathways and interactions. We posit that co-transcriptional folding of these transcripts ultimately dictates their downstream functions. Elucidating the spatiotemporal folding of non-coding RNAs during transcription therefore provides invaluable insights into bacterial pathogeneses and predictive disease diagnostics. Finally, we discuss the implications of co-transcriptional folding andapplications of RNAs for therapeutics and drug targets. In this review, Chauvier and Walter summarize our current understanding of bacterial non-coding RNAs such as riboswitches and small RNAs, from gene regulation to their promise as therapeutic targets and disease biomarkers. Furthermore, the authors discuss the importance of the kinetic events during co-transcriptional RNA folding that enable regulatory function. [ABSTRACT FROM AUTHOR]

G-quadruplexes (G4s) are stable, noncanonical structures formed in guanine (G)-rich sequences of DNA/RNA. G4 structures are reported to play a regulatory role in various cellular processes and, recently, a considerable number of studies have attributed new biological functions to these structures, especially in RNA. Noncoding RNA (ncRNA), which does not translate into a functional protein, is widely expressed and has been shown to play a key role in shaping cellular activity. There has been growing evidence of G4 formation in several ncRNA classes, and it has been identified as a key part for diverse biological functions and physio-pathological contexts in neurodegenerative diseases and cancer. This review discusses RNA G4s (rG4s) in ncRNA, focusing on the molecular mechanism underlying its function. This review also aims to highlight potential and emerging opportunities to identify and target the rG4s in ncRNA to understand its function and, ultimately, treat many diseases. [Display omitted] G-quadruplex (G4) are stable, non-canonical structures formed in DNA/RNA by guanine-rich sequences and reported to play a regulatory role in various cellular processes. In this review, Vinodh et al. highlight the role and function of G4 structures in non-coding RNA and emerging opportunities to identify and target those structures. [ABSTRACT FROM AUTHOR]

Non-coding RNAs, including microRNAs, long non-coding RNAs, and circular RNAs, have been identified as crucial regulators of various biological processes through epigenetic regulation, transcriptional regulation, and post-transcriptional regulation. Growing evidence suggests that dysregulation and activation of non-coding RNAs are closely associated with tumor angiogenesis, a process essential for tumor growth and metastasis and a major contributor to cancer-related mortality. Therefore, understanding the molecular mechanisms underlying tumor angiogenesis is of utmost importance. Numerous studies have documented the involvement of different types of non-coding RNAs in the regulation of angiogenesis. This review provides an overview of how non-coding RNAs regulate tumor angiogenesis. Additionally, we discuss emerging strategies that exploit non-coding RNAs for anti-angiogenic therapy in cancer treatment. Ultimately, this review underscores the crucial role played by non-coding RNAs in tumor angiogenesis and highlights their potential as therapeutic targets for anti-angiogenic interventions against cancer. [ABSTRACT FROM AUTHOR]

RNA biology has risen to prominence after a remarkable discovery of diverse functions of noncoding RNA (ncRNA). Most untranslated transcripts often exert their regulatory functions into RNA–RNA complexes via base pairing with complementary sequences in other RNAs. An interplay between RNAs is essential, as it possesses various functional roles in human cells, including genetic translation, RNA splicing, editing, ribosomal RNA maturation, RNA degradation and the regulation of metabolic pathways/riboswitches. Moreover, the pervasive transcription of the human genome allows for the discovery of novel genomic functions via RNA interactome investigation. The advancement of experimental procedures has resulted in an explosion of documented data, necessitating the development of efficient and precise computational tools and algorithms. This review provides an extensive update on RNA–RNA interaction (RRI) analysis via thermodynamic- and comparative-based RNA secondary structure prediction (RSP) and RNA–RNA interaction prediction (RIP) tools and their general functions. We also highlighted the current knowledge of RRIs and the limitations of RNA interactome mapping via experimental data. Then, the gap between RSP and RIP, the importance of RNA homologues, the relationship between pseudoknots, and RNA folding thermodynamics are discussed. It is hoped that these emerging prediction tools will deepen the understanding of RNA-associated interactions in human diseases and hasten treatment processes. [ABSTRACT FROM AUTHOR]

Zinc finger protein 217 (ZNF217) is one of the well-researched members of the Krüppel-like factor transcription factor family. ZNF217 possesses a characteristic structure of zinc finger motifs and plays a crucial role in regulating the biological activities of cells. Recent findings have revealed that ZNF217 is strongly associated with multiple aspects of cancer progression, impacting patient prognosis. Notably, ZNF217 is subject to regulation by non-coding RNAs, suggesting the potential for targeted manipulation of such RNAs as a robust therapeutic avenue for managing cancer in the future. The main purpose of this article is to provide a detailed examination of the role of ZNF217 in human malignant tumors and the regulation of its expression, and to offer new perspectives for cancer treatment. [ABSTRACT FROM AUTHOR]

The pituitary gland serves as the central endocrine regulator of growth, reproduction, and metabolism and plays a crucial role in the reproductive process of female animals. Transcriptome analysis was conducted using pituitary gland samples from Leizhou goats with varying levels of fecundity to investigate the effects of long noncoding RNA (lncRNA), circular RNA (circRNA), and mRNA regulation on pituitary hormone secretion and its association with goat fecundity. The analysis aimed to identify lncRNAs, circRNAs, and mRNAs that influence the fertility of Leizhou goats. GO and KEGG enrichment analyses were performed on differentially expressed lncRNAs, circRNAs, and mRNAs and revealed considerable enrichment in pathways, such as regulation of hormone secretion, germ cell development, and gonadotropin-releasing hormone secretion. The pituitary lncRNAs (ENSCHIT00000010293, ENSCHIT00000010304, ENSCHIT00000010306, ENSCHIT00000010290, ENSCHIT00000010298, ENSCHIT00000006769, ENSCHIT00000006767, ENSCHIT00000006921, and ENSCHIT00000001330) and circRNAs (chicirc_ 029285, chicirc_026618, chicirc_129655, chicirc_018248, chicirc_122554, chicirc_087101, and chicirc_078945) identified as differentially expressed regulated hormone secretion in the pituitary through their respective host genes. Additionally, differential mRNAs (GABBR2, SYCP1, HNF4A, CBLN1, and CDKN1A) influenced goat fecundity by affecting hormone secretion in the pituitary gland. These findings contribute to the understanding of the molecular mechanisms underlying pituitary regulation of fecundity in Leizhou goats. [ABSTRACT FROM AUTHOR]

Fetal growth restriction (FGR) is associated with impaired angiogenesis and chronic inflammation. MicroRNAs (miRs) are short noncoding RNAs that regulate gene expression at the post-transcriptional level by targeting messenger RNA (mRNA) for degradation or by suppressing translation. We hypothesize that dysregulation of miR-15b, an antiangiogenic miR, and miR-146a, an anti-inflammatory miR, are associated with the FGR's pathogenesis. Pregnant mice were provided ad libitum access to food between E1 and E8. From E9-E18, dams received either a 50% caloric restricted diet (FGR) or continued ad libitum access (controls). Placentas were harvested at E18.5 and total RNA was extracted. Gene expression levels of miRs and mRNAs were compared between FGR and control placentas. Placentas affected by FGR demonstrated increased expression of miR-15b. Vascular endothelial growth factor alpha, which is downregulated in response to increased levels of miR-15b, was suppressed. The anti-inflammatory miR, miR-146a, was downregulated, resulting in upregulation of proinflammatory (IL-6, IL-8, and NFkB1) and oxidative stress (HIF-1α, SOD2, and Nox2) mediators. Aberrant angiogenesis and chronic inflammation seen in FGR appear to be associated with dysregulated miR-15b and miR-146a gene expression, respectively. This observation suggests these miRs play a post-transcriptional regulatory role in FGR, providing an insight into possible therapeutic targets. [ABSTRACT FROM AUTHOR]

Noncoding RNAs constitute a substantial portion of the transcriptome and play pivotal roles in plant growth and development. Among these processes, flowering stands out as a crucial trait, ensuring reproductive success and seed set, and is meticulously controlled by genetic and environmental factors. With remarkable advancements in the identification and characterization of noncoding RNAs in plants, it has become evident that noncoding RNAs are intricately linked to the regulation of flowering time. In this article, we present an overview of the classification of plant noncoding RNAs and delve into their functions in the regulation of flowering time. Furthermore, we review their molecular mechanisms and their involvement in flowering pathways. Our comprehensive review enhances the understanding of how noncoding RNAs contribute to the regulation of flowering time and sheds light on their potential implications in crop breeding. [ABSTRACT FROM AUTHOR]

Fighting cancer remains one of the greatest challenges for science in the 21st century. Advances in immunotherapy against different types of cancer have greatly contributed to the treatment, remission, and cure of patients. In this context, knowledge of epigenetic phenomena, their relationship with tumor cells and how the immune system can be epigenetically modulated represent some of the greatest advances in the development of anticancer therapies. Epigenetics is a rapidly growing field that studies how environmental factors can affect gene expression without altering DNA sequence. Epigenomic changes include DNA methylation, histone modifications, and non-coding RNA regulation, which impact cellular function. Epigenetics has shown promise in developing cancer therapies, such as immunotherapy, which aims to stimulate the immune system to attack cancer cells. For example, PD-1 and PD-L1 are biomarkers that regulate the immune response to cancer cells and recent studies have shown that epigenetic modifications can affect their expression, potentially influencing the efficacy of immunotherapy. New therapies targeting epigenetic modifications, such as histone deacetylases and DNA methyltransferases, are being developed for cancer treatment, and some have shown promise in preclinical studies and clinical trials. With growing understanding of epigenetic regulation, we can expect more personalized and effective cancer immunotherapies in the future. This review highlights key advances in the use of epigenetic and epigenomic tools and modern immuno-oncology strategies to treat several types of tumors. [ABSTRACT FROM AUTHOR]

BACKGROUND: Neuronal cell apoptosis after spinal cord injury is a major cause of permanent spinal cord injury. It is of great significance to explore ways to prevent neuronal apoptosis after spinal cord injury. Existing animal experiments have shown that non-coding RNA can regulate neuronal apoptosis after spinal cord injury, which may provide a certain reference for clinical neuronal protective therapy after spinal cord injury. OBJECTIVE: To review the role and mechanism of non-coding RNA in regulating neuronal apoptosis after spinal cord injury so as to provide a new target for protective treatment of spinal cord injury. METHODS: Search terms “microRNA, miR, lncRNA, circRNA, noncoding RNA, RNA, SCI, spinal cord injury, spinal cord, apoptosis” were searched in the PubMed database. The inclusion and exclusion criteria were formulated, and 87 relevant articles were included by reading the title, abstract and full text. RESULTS AND CONCLUSION: (1) Neuronal cell apoptosis is an important pathophysiological change in secondary spinal cord injury, and it is an important mechanism of neuronal death and spinal cord dysfunction. (2) Animal experiments showed that miRNA, lncRNA and circRNA related to neuronal cell apoptosis were significantly differentially expressed in spinal cord tissues after spinal cord injury, and some miRNA, lncRNA and circRNA that promoted neuronal apoptosis were overexpressed. The expression of miRNA, lncRNA and circRNA that inhibited neuronal apoptosis was down-regulated. (3) By regulating the corresponding expression of specific miRNA, the excessive apoptosis of neuronal cells after spinal cord injury can be inhibited mainly by down-regulating the apoptotic gene Bax, inhibiting the TLR4/nuclear factor-κB signaling pathway, and activating the PI3K/Akt signaling pathway. (4) The regulation of lncRNA and circRNA expression mainly causes the silencing or overexpression of specific miRNA by targeting negative regulation, so as to exert its anti-neuronal apoptosis effect. (5) Among miRNAs, miR-125b can regulate Smurf1/KLF2/ATF2 axis and JAK1/STAT1 signaling pathway, while miR-21-5p can regulate programmed cell death factor 4 (PDCD4) and PI3K/AKT signaling pathway, showing multi-pathway anti-apoptotic effect. (6) Among lncRNAs and circRNAs, lncRNA-PTENP1, lncRNA-TCTN2 and circRNA-HIPK3 have targeted regulatory effects on a variety of miRNAs. These non-coding RNAs may become new targets for neuronal protective therapy after spinal cord injury. (7) At the moment, non-coding RNA regulation of neuronal apoptosis after spinal cord injury also only stays in animal cells. In the future, we need to continue to explore more targeted non-coding RNA drug carriers, joint biological tissue engineering as well as other emerging technologies, and strive for an early transition to clinical transformation. [ABSTRACT FROM AUTHOR]

Atherosclerosis is the leading cause of numerous cardiovascular diseases with a high mortality rate. Non-coding RNAs (ncRNAs), RNA molecules that do not encode proteins in human genome transcripts, are known to play crucial roles in various physiological and pathological processes. Recently, researches on the regulation of atherosclerosis by ncRNAs, mainly including microRNAs, long noncoding RNAs, and circular RNAs, have gradually become a hot topic. Traditional Chinese medicine has been proved to be effective in treating cardiovascular diseases in China for a long time, and its active monomers have been found to target a variety of atherosclerosis-related ncRNAs. These active monomers of traditional Chinese medicine hold great potential as drugs for the treatment of atherosclerosis. Here, we summarized current advancement of the molecular pathways by which ncRNAs regulate atherosclerosis and mainly highlighted the mechanisms of traditional Chinese medicine monomers in regulating atherosclerosis through targeting ncRNAs. [ABSTRACT FROM AUTHOR]

Dynamic tuning of the poly(A) tail is a crucial mechanism for controlling translation and stability of eukaryotic mRNA. Achieving a comprehensive understanding of how this regulation occurs requires unbiased abundance quantification of poly(A)-tail transcripts and simple poly(A)-length measurement using high-throughput sequencing platforms. Current methods have limitations due to complicated setups and elaborate library preparation plans. To address this, we introduce central limit theorem (CLT)–managed RNA-seq (CLT-seq), a simple and straightforward homopolymer-sequencing method. In CLT-seq, an anchor-free oligo(dT) primer rapidly binds to and unbinds from anywhere along the poly(A) tail string, leading to position-directed reverse transcription with equal probability. The CLT mechanism enables the synthesized poly(T) lengths, which correspond to the templated segment of the poly(A) tail, to distribute normally. Based on a well-fitted pseudogaussian-derived poly(A)-poly(T) conversion model, the actual poly(A)-tail profile is reconstructed from the acquired poly(T)-length profile through matrix operations. CLT-seq follows a simple procedure without requiring RNA-related pre-treatment, enrichment or selection, and the CLT-shortened poly(T) stretches are more compatible with existing sequencing platforms. This proof-of-concept approach facilitates direct homopolymer base-calling and features unbiased RNA-seq. Therefore, CLT-seq provides unbiased, robust and cost-efficient transcriptome-wide poly(A)-tail profiling. We demonstrate that CLT-seq on the most common Illumina platform delivers reliable poly(A)-tail profiling at a transcriptome-wide scale in human cellular contexts. We find that the poly(A)-tail-tuned ncRNA regulation undergoes a dynamic, complex process similar to mRNA regulation. Overall, CLT-seq offers a simplified, effective and economical approach to investigate poly(A)-tail regulation, with potential implications for understanding gene expression and identifying therapeutic targets. [ABSTRACT FROM AUTHOR]

The increasing demand for food is the result of an increasing population. It is crucial to enhance crop yield for sustainable production. Recently, microRNAs (miRNAs) have gained importance because of their involvement in crop productivity by regulating gene transcription in numerous biological processes, such as growth, development and abiotic and biotic stresses. miRNAs are small, non-coding RNA involved in numerous other biological functions in a plant that range from genomic integrity, metabolism, growth, and development to environmental stress response, which collectively influence the agronomic traits of the crop species. Additionally, miRNA families associated with various agronomic properties are conserved across diverse plant species. The miRNA adaptive responses enhance the plants to survive environmental stresses, such as drought, salinity, cold, and heat conditions, as well as biotic stresses, such as pathogens and insect pests. Thus, understanding the detailed mechanism of the potential response of miRNAs during stress response is necessary to promote the agronomic traits of crops. In this review, we updated the details of the functional aspects of miRNAs as potential regulators of various stress-related responses in agronomic plants. [ABSTRACT FROM AUTHOR]

Flagella are important for bacterial motility as well as for pathogenesis. Synthesis of these structures is energy intensive and, while extensive transcriptional regulation has been described, little is known about the posttranscriptional regulation. Small RNAs (sRNAs) are widespread posttranscriptional regulators, most base pairing with mRNAs to affect their stability and/or translation. Here, we describe four UTR-derived sRNAs (UhpU, MotR, FliX and FlgO) whose expression is controlled by the flagella sigma factor σ28 (fliA) in Escherichia coli. Interestingly, the four sRNAs have varied effects on flagellin protein levels, flagella number and cell motility. UhpU, corresponding to the 3' UTR of a metabolic gene, likely has hundreds of targets including a transcriptional regulator at the top flagella regulatory cascade connecting metabolism and flagella synthesis. Unlike most sRNAs, MotR and FliX base pair within the coding sequences of target mRNAs and act on ribosomal protein mRNAs connecting ribosome production and flagella synthesis. The study shows how sRNA-mediated regulation can overlay a complex network enabling nuanced control of flagella synthesis. [ABSTRACT FROM AUTHOR]

RNA-RNA interactions play a crucial role in regulating gene expression and various biological processes, but identifying these interactions on a transcriptomic scale remains a challenge. To address this, we have developed a new biochemical technique called pCp-biotin labelled RNA hybrid and ultraviolet crosslinking and immunoprecipitation (lhCLIP) that enables the transcriptome-wide identification of intra- and intermolecular RNA-RNA interactions mediated by a specific RNA-binding protein (RBP). Using lhCLIP, we have uncovered a diverse landscape of intermolecular RNA interactions recognized by hnRNPK in human cells, involving all major classes of noncoding RNAs (ncRNAs) and mRNA. Notably, hnRNPK selectively binds with snRNA U4, U11, and U12, and shapes the secondary structure of these snRNAs, which may impact RNA splicing. Our study demonstrates the potential of lhCLIP as a user-friendly and widely applicable method for discovering RNA-RNA interactions mediated by a particular protein of interest and provides a valuable tool for further investigating the role of RBPs in gene expression and biological processes. Author summary: RBPs play a crucial role in post-transcriptional regulation of RNAs by modulating RNA-RNA interactions, encompassing processes like pre-mRNA splicing and mRNA degradation. Existing techniques for exploring RNA interactions associated with specific RBPs require some troublesome experimental procedures, including the use of radioisotopes to visualize RBP-RNA complexes and the introduction of exogenous expression of the target protein. In this context, we introduce lhCLIP, a novel method designed for capturing RNA-RNA interactions mediated by a specific protein. Diverging from other approaches reliant on radioisotopes, lhCLIP eliminates the need for their use. Moreover, its heightened sensitivity enables the capture of RNA-RNA interactions mediated by endogenously expressed RBPs, making it an intuitive and competitive option for researchers. We utilized lhCLIP to investigate RNA hybrids that are directly bound by hnRNPK, unveiling a complex array of intra- and intermolecular RNA interactions with the potential to exert influence over RNA splicing. [ABSTRACT FROM AUTHOR]

Simple Summary: Viral outbreaks continue to be an obstacle to human health, with the Severe Acute Respiratory Syndrome-related Coronavirus (SARS-CoV-2) pandemic shedding light on the current vulnerabilities of our healthcare system. Understanding viral pathology is paramount in developing methods to combat infection. The study of microRNAs (miRNAs) is relatively new to the world of virology research. These small strands of nucleotides are a versatile tool in the regulation of gene expression. Various miRNAs have roles in immune development, immune and inflammatory responses, and viral infections. Changes in miRNA expression can be a double-edged sword, used to alter cell activities to help the host fight infections or taken advantage of by viruses to enhance infection. Uncovering these interactions and their implications can provide direction for therapeutic and diagnostic advancement. Further, miRNAs may have the potential to predict the severity of viral infection and possible health outcomes, as well as track disease progression to inform treatment options. miRNA technology is also anticipated to be highly marketable and has already entered the realm of commercial biopharmaceuticals. Continuing to elucidate the functions of miRNA during infection and the therapeutic potential of these molecules will contribute to new strategies in the battle against current and future viral pathogens. Since the discovery of microRNAs (miRNAs) in C. elegans in 1993, the field of miRNA research has grown steeply. These single-stranded non-coding RNA molecules canonically work at the post-transcriptional phase to regulate protein expression. miRNAs are known to regulate viral infection and the ensuing host immune response. Evolving research suggests miRNAs are assets in the discovery and investigation of therapeutics and diagnostics. In this review, we succinctly summarize the latest findings in (i) mechanisms underpinning miRNA regulation of viral infection, (ii) miRNA regulation of host immune response to viral pathogens, (iii) miRNA-based diagnostics and therapeutics targeting viral pathogens and challenges, and (iv) miRNA patents and the market landscape. Our findings show the differential expression of miRNA may serve as a prognostic biomarker for viral infections in regard to predicting the severity or adverse health effects associated with viral diseases. While there is huge market potential for miRNA technology, the novel approach of using miRNA mimics to enhance antiviral activity or antagonists to inhibit pro-viral miRNAs has been an ongoing research endeavor. Significant hurdles remain in terms of miRNA delivery, stability, efficacy, safety/tolerability, and specificity. Addressing these challenges may pave a path for harnessing the full potential of miRNAs in modern medicine. [ABSTRACT FROM AUTHOR]

Noncoding RNAs (ncRNAs) are active regulators of a wide range of biological and physiological processes, including the majority of mammalian reproductive events. Knowledge of the biological activities of ncRNAs in the context of mammalian reproduction will allow for a more comprehensive and comparative understanding of male sterility and fertility. In this review, we describe recent advances in ncRNA‐mediated control of mammalian reproduction and emphasize the importance of ncRNAs in several aspects of mammalian reproduction, such as germ cell biogenesis and reproductive organ activity. Furthermore, we focus on gene expression regulatory feedback loops including hormones and ncRNA expression to better understand germ cell commitment and reproductive organ function. Finally, this study shows the role of ncRNAs in male reproductive failure and provides suggestions for further research. Significance statement: The importance of noncoding RNAs (ncRNAs) in various aspects of mammalian reproduction, including germ cell biogenesis, the functionality of reproductive organs, the development of the early embryo, and infertility and sterility caused on by ncRNA dysregulation in both males and females, are highlighted in this paper's summary of recent developments in microRNAs (miRNA)‐mediated regulation of mammalian reproduction. spermatogenesis and spermatogonial differentiation are in their very early stages, testicular miRNA expression is shown to change significantly. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs have gained attention in recent years as they were shown to play crucial roles in the regulation of cellular processes, but the understanding of the exact mechanisms is still incomplete in most cases. This is also true for long non-coding RNA LINC00941, which was recently found to be highly upregulated in various types of cancer influencing cell proliferation and metastasis. Initial studies could not elucidate the mode of action to understand the role and real impact of LINC00941 in tissue homeostasis and cancer development. However, recent analyses have demonstrated multiple potential modes of action of LINC00941 influencing the functionality of various cancer cell types. Correspondingly, LINC00941 was proposed to be involved in regulation of mRNA transcription and modulation of protein stability, respectively. In addition, several experimental approaches suggest a function of LINC00941 as competitive endogenous RNA, thus acting in a post-transcriptional regulatory fashion. This review summarizes our recent knowledge about the mechanisms of action of LINC00941 elucidated so far and discusses its putative role in miRNA sequestering processes. In addition, the functional role of LINC00941 in regulating human keratinocytes is discussed to also highlight its role in normal tissue homeostasis tissue aside from its involvement in cancer. [ABSTRACT FROM AUTHOR]