Non-coding RNA Transcripts Research Articles

Core Promoter Regions of Antisense and Long Intergenic Non-Coding RNAs.

RNA polymerase II (POL II) is responsible for the transcription of messenger RNAs (mRNAs) and long non-coding RNAs (lncRNAs). Previously, we have shown the evolutionary invariance of the structural features of DNA in the POL II core promoters of the precursors of mRNAs. In this work, we have analyzed the POL II core promoters of the precursors of lncRNAs in Homo sapiens and Mus musculus genomes. Structural analysis of nucleotide sequences in positions -50, +30 bp in relation to the TSS have shown the extremely heterogeneous 3D structure that includes two singular regions - hexanucleotide "INR" around the TSS and octanucleotide "TATA-box" at around ~-28 bp upstream. Thus, the 3D structure of core promoters of lncRNA resembles the architecture of the core promoters of mRNAs; however, textual analysis revealed differences between promoters of lncRNAs and promoters of mRNAs, which lies in their textual characteristics; namely, the informational entropy at each position of the nucleotide text of lncRNA core promoters (by the exception of singular regions) is significantly higher than that of the mRNA core promoters. Another distinguishing feature of lncRNA is the extremely rare occurrence in the TATA box of octanucleotides with the consensus sequence. These textual differences can significantly affect the efficiency of the transcription of lncRNAs.

Decreased RNA polymerase III subunit expression leads to defects in oligodendrocyte development.

RNA polymerase III (Pol III) is a critical enzymatic complex tasked with the transcription of ubiquitous non-coding RNAs including 5S rRNA and all tRNA genes. Despite the constitutive nature of this enzyme, hypomorphic biallelic pathogenic variants in genes encoding subunits of Pol III lead to tissue-specific features and cause a hypomyelinating leukodystrophy, characterized by a severe and permanent deficit in myelin. The pathophysiological mechanisms in POLR3- related leukodystrophy and specifically, how reduced Pol III function impacts oligodendrocyte development to account for the devastating hypomyelination seen in the disease, remain poorly understood. In this study, we characterize how reducing endogenous transcript levels of leukodystrophy-associated Pol III subunits affects oligodendrocyte maturation at the level of their migration, proliferation, differentiation, and myelination. Our results show that decreasing Pol III expression altered the proliferation rate of oligodendrocyte precursor cells but had no impact on migration. Additionally, reducing Pol III activity impaired the differentiation of these precursor cells into mature oligodendrocytes, evident at both the level of OL-lineage marker expression and on morphological assessment, with Pol III knockdown cells displaying a drastically more immature branching complexity. Myelination was hindered in the Pol III knockdown cells, as determined in both organotypic shiverer slice cultures and co-cultures with nanofibers. Analysis of Pol III transcriptional activity revealed a decrease in the expression of distinct tRNAs, which was significant in the siPolr3a condition. In turn, our findings provide insight into the role of Pol III in oligodendrocyte development and shed light on the pathophysiological mechanisms of hypomyelination in POLR3-related leukodystrophy.

Flap endonuclease Rad27 cleaves the RNA of R-loop structures to suppress telomere recombination.

The long non-coding telomeric RNA transcript TERRA, in the form of an RNA-DNA duplex, regulates telomere recombination. In a screen for nucleases that affects telomere recombination, mutations in DNA2, EXO1, MRE11 and SAE2 cause severe delay in type II survivor formation, indicating that type II telomere recombination is mediated through a mechanism similar to repairing double-strand breaks. On the other hand, mutation in RAD27 results in early formation of type II recombination, suggesting that RAD27 acts as a negative regulator in telomere recombination. RAD27 encodes a flap endonuclease that plays a role in DNA metabolism, including replication, repair and recombination. We demonstrate that Rad27 suppresses the accumulation of the TERRA-associated R-loop and selectively cleaves TERRA of R-loop and double-flapped structures in vitro. Moreover, we show that Rad27 negatively regulates single-stranded C-rich telomeric DNA circles (C-circles) in telomerase-deficient cells, revealing a close correlation between R-loop and C-circles during telomere recombination. These results demonstrate that Rad27 participates in telomere recombination by cleaving TERRA in the context of an R-loop or flapped RNA-DNA duplex, providing mechanistic insight into how Rad27 maintains chromosome stability by restricting the accumulation of the R-loop structure within the genome.

CircRNAs and RNA-Binding Proteins Involved in the Pathogenesis of Cancers or Central Nervous System Disorders.

Circular RNAs (circRNAs), a newly recognized group of noncoding RNA transcripts, have established widespread attention due to their regulatory role in cell signaling. They are covalently closed noncoding RNAs that form a loop, and are typically generated during the splicing of precursor RNAs. CircRNAs are key post-transcriptional and post-translational regulators of gene expression programs that might influence cellular response and/or function. In particular, circRNAs have been considered to function as sponges of specific miRNA, regulating cellular processes at the post-transcription stage. Accumulating evidence has shown that the aberrant expression of circRNAs could play a key role in the pathogenesis of several diseases. Notably, circRNAs, microRNAs, and several RNA-binding proteins, including the antiproliferative (APRO) family proteins, could be indispensable gene modulators, which might be strongly linked to the occurrence of diseases. In addition, circRNAs have attracted general interest for their stability, abundance in the brain, and their capability to cross the blood-brain barrier. Here, we present the current findings and theragnostic potentials of circRNAs in several diseases. With this, we aim to provide new insights to support the development of novel diagnostic and/or therapeutic strategies for these diseases.

Aberrant lncRNA expression in patients with proliferative diabetic retinopathy: preliminary results from a single-center observational study

BackgroundDiabetic retinopathy (DR) is a leading cause of blindness. Vision threat is particularly severe in patients with retinal neovascularization. However, little is known about the role of long noncoding RNAs (lncRNAs) in proliferative diabetic retinopathy (PDR). The goal of this study was to identify lncRNAs involved in PDR.MethodsWe compared lncRNA expression profiles in the vitreous between patients with PDR and those with idiopathic macular hole (IMH) and between patients with PDR who had received anti-vascular endothelial growth factor (VEGF) therapy and those who had not. Vitreous samples from patients with PDR and IMH were screened for lncRNAs using microarray-based analysis, and quantitative real-time polymerase chain reaction (qRT-PCR) was used to confirm the microarray results. Bioinformatic analysis was also performed. Moreover, the effect of anti-VEGF therapy was investigated in vitreous samples of patients with PDR treated with anti-VEGF therapy and those who were not.ResultsA total of 1067 differentially expressed noncoding RNA transcripts were found during screening in the vitreous humor of patients with PDR than in those with IMH. Five lncRNAs were subjected to qRT-PCR. RP11-573 J24.1, RP11-787B4.2, RP11-654G14.1, RP11-2A4.3, and RP11-502I4.3 were significantly downregulated; this was validated by the comparison using the microarray data. In addition, 835 differentially expressed noncoding RNA transcripts were found during screening in the vitreous humor of patients with PDR treated with anti-VEGF therapy compared with untreated PDR patients. RP4-631H13.2 was significantly upregulated, which is consistent with the trend of the microarray analysis.ConclusionsThere were systemic expression differences in the vitreous at the microarray level between patients with PDR and those with IMH and between patients with PDR after anti-VEGF treatment and those that did not receive anti-VEGF treatment. LncRNAs identified in the vitreous humor may be a novel research field for PDR.

LncRNA-MALAT1: A Key Participant in the Occurrence and Development of Cancer.

LncRNAs are a group of non-coding RNA transcripts with lengths of over 200 nucleotides and can interact with DNA, RNA, and proteins to regulate gene expression of malignant tumors in human tissues. LncRNAs participate in vital processes, such as chromosomal nuclear transport in the cancerous site of human tissue, activation, and the regulation of proto-oncogenes, the differentiation of immune cells, and the regulation of the cellular immune system. The lncRNA metastasis-associated lung cancer transcript 1 (MALAT1) is reportedly involved in the occurrence and development of many cancers and serves as a biomarker and therapeutic target. These findings highlight its promising role in cancer treatment. In this article, we comprehensively summarized the structure and functions of lncRNA, notably the discoveries of lncRNA-MALAT1 in different cancers, the action mechanisms, and the ongoing research on new drug development. We believe our review would serve as a basis for further research on the pathological mechanism of lncRNA-MALAT1 in cancer and provide evidence and novel insights into its application in clinical diagnoses and treatments.

Long Noncoding RNA Expression Independently Predicts Outcome in Pediatric Acute Myeloid Leukemia.

Optimized strategies for risk classification are essential to tailor therapy for patients with biologically distinctive disease. Risk classification in pediatric acute myeloid leukemia (pAML) relies on detection of translocations and gene mutations. Long noncoding RNA (lncRNA) transcripts have been shown to associate with and mediate malignant phenotypes in acute myeloid leukemia (AML) but have not been comprehensively evaluated in pAML. To identify lncRNA transcripts associated with outcomes, we evaluated the annotated lncRNA landscape by transcript sequencing of 1,298 pediatric and 96 adult AML specimens. Upregulated lncRNAs identified in the pAML training set were used to establish a regularized Cox regression model of event-free survival (EFS), yielding a 37 lncRNA signature (lncScore). Discretized lncScores were correlated with initial and postinduction treatment outcomes using Cox proportional hazards models in validation sets. Predictive model performance was compared with standard stratification methods by concordance analysis. Training set cases with positive lncScores had 5-year EFS and overall survival rates of 26.7% and 42.7%, respectively, compared with 56.9% and 76.3% with negative lncScores (hazard ratio, 2.48 and 3.16; P < .001). Pediatric validation cohorts and an adult AML group yielded comparable results in magnitude and significance. lncScore remained independently prognostic in multivariable models, including key factors used in preinduction and postinduction risk stratification. Subgroup analysis suggested that lncScores provide additional outcome information in heterogeneous subgroups currently classified as indeterminate risk. Concordance analysis showed that lncScore adds to overall classification accuracy with at least comparable predictive performance to current stratification methods that rely on multiple assays. Inclusion of the lncScore enhances predictive power of traditional cytogenetic and mutation-defined stratification in pAML with potential, as a single assay, to replace these complex stratification schemes with comparable predictive accuracy.

Longevity, Centenarians and Modified Cellular Proteodynamics.

We have shown before that at least one intracellular proteolytic system seems to be at least as abundant in the peripheral blood lymphocytes of centenarians as in the same cells of young individuals (with the cells of the elderly population showing a significant dip compared to both young and centenarian cohorts). Despite scarce published data, in this review, we tried to answer the question how do different types of cells of longevous people-nonagenarians to (semi)supercentenarians-maintain the quality and quantity of their structural and functional proteins? Specifically, we asked if more robust proteodynamics participate in longevity. We hypothesized that at least some factors controlling the maintenance of cellular proteomes in centenarians will remain at the "young" level (just performing better than in the average elderly). In our quest, we considered multiple aspects of cellular protein maintenance (proteodynamics), including the quality of transcribed DNA, its epigenetic changes, fidelity and quantitative features of transcription of both mRNA and noncoding RNAs, the process of translation, posttranslational modifications leading to maturation and functionalization of nascent proteins, and, finally, multiple facets of the process of elimination of misfolded, aggregated, and otherwise dysfunctional proteins (autophagy). We also included the status of mitochondria, especially production of ATP necessary for protein synthesis and maintenance. We found that with the exception of the latter and of chaperone function, practically all of the considered aspects did show better performance in centenarians than in the average elderly, and most of them approached the levels/activities seen in the cells of young individuals.

Cortical interneuron development is affected in 4H leukodystrophy.

4H leukodystrophy is a rare genetic disorder classically characterized by hypomyelination, hypodontia and hypogonadotropic hypogonadism. With the discovery that 4H is caused by mutations that affect RNA polymerase III, mainly involved in the transcription of small non-coding RNAs, patients with atypical presentations with mainly a neuronal phenotype were also identified. Pathomechanisms of 4H brain abnormalities are still unknown and research is hampered by a lack of preclinical models. We aimed to identify cells and pathways that are affected by 4H mutations using induced pluripotent stem cell models. RNA sequencing analysis on induced pluripotent stem cell-derived cerebellar cells revealed several differentially expressed genes between 4H patients and control samples, including reduced ARX expression. As ARX is involved in early brain and interneuron development, we studied and confirmed interneuron changes in primary tissue of 4H patients. Subsequently, we studied interneuron changes in more depth and analysed induced pluripotent stem cell-derived cortical neuron cultures for changes in neuronal morphology, synaptic balance, network activity and myelination. We showed a decreased percentage of GABAergic synapses in 4H, which correlated to increased neuronal network activity. Treatment of cultures with GABA antagonists led to a significant increase in neuronal network activity in control cells but not in 4H cells, also pointing to lack of inhibitory activity in 4H. Myelination and oligodendrocyte maturation in cultures with 4H neurons was normal, and treatment with sonic hedgehog agonist SAG did not improve 4H related neuronal phenotypes. Quantitative PCR analysis revealed increased expression of parvalbumin interneuron marker ERBB4, suggesting that the development rather than generation of interneurons may be affected in 4H. Together, these results indicate that interneurons are involved, possibly parvalbumin interneurons, in disease mechanisms of 4H leukodystrophy.

Promoter‐pervasive transcription causes RNA polymerase II pausing to boost DOG1 expression in response to salt

Eukaryotic genomes are pervasively transcribed by RNA polymerase II. Yet, the molecular and biological implications of such a phenomenon are still largely puzzling. Here, we describe noncoding RNA transcription upstream of the Arabidopsis thaliana DOG1 gene, which governs salt stress responses and is a key regulator of seed dormancy. We find that expression of the DOG1 gene is induced by salt stress, thereby causing a delay in seed germination. We uncover extensive transcriptional activity on the promoter of the DOG1 gene, which produces a variety of lncRNAs. These lncRNAs, named PUPPIES, are co‐directionally transcribed and extend into the DOG1 coding region. We show that PUPPIES RNAs respond to salt stress and boost DOG1 expression, resulting in delayed germination. This positive role of pervasive PUPPIES transcription on DOG1 gene expression is associated with augmented pausing of RNA polymerase II, slower transcription and higher transcriptional burst size. These findings highlight the positive role of upstream co‐directional transcription in controlling transcriptional dynamics of downstream genes.

Protein-Coding Region Derived Small RNA in Exosomes from Influenza A Virus-Infected Cells.

Exosomes may function as multifactorial mediators of cell-to-cell communication, playing crucial roles in both physiological and pathological processes. Exosomes released from virus-infected cells may contain RNA and proteins facilitating infection spread. The purpose of our study was to analyze how the small RNA content of exosomes is affected by infection with the influenza A virus (IAV). Exosomes were isolated by ultracentrifugation after hemadsorption of virions and their small RNA content was identified using high-throughput sequencing. As compared to mock-infected controls, 856 RNA transcripts were significantly differentially expressed in exosomes from IAV-infected cells, including fragments of 458 protein-coding (pcRNA), 336 small, 28 long intergenic non-coding RNA transcripts, and 33 pseudogene transcripts. Upregulated pcRNA species corresponded mainly to proteins associated with translation and antiviral response, and the most upregulated among them were RSAD2, CCDC141 and IFIT2. Downregulated pcRNA species corresponded to proteins associated with the cell cycle and DNA packaging. Analysis of differentially expressed pseudogenes showed that in most cases, an increase in the transcription level of pseudogenes was correlated with an increase in their parental genes. Although the role of exosome RNA in IAV infection remains undefined, the biological processes identified based on the corresponding proteins may indicate the roles of some of its parts in IAV replication.

Spt4 promotes cellular senescence by activating non-coding RNA transcription in ribosomal RNA gene clusters

Genome instability can drive aging in many organisms. The ribosomal RNA gene (rDNA) cluster is one of the most unstable regions in the genome and the stability of this region impacts replicative lifespan in budding yeast. To understand the underlying mechanism, we search for yeast mutants with stabler rDNA and longer lifespans than wild-type cells. We show that absence of a transcription elongation factor, Spt4, results in increased rDNA stability, reduced levels of non-coding RNA transcripts from the regulatory E-pro promoter in the rDNA, and extended replicative lifespan in a SIR2-dependent manner. Spt4-dependent lifespan restriction is abolished in the absence of non-coding RNA transcription at the E-pro locus. The amount of Spt4 increases and its function becomes more important as cells age. These findings suggest that Spt4 is a promising aging factor that accelerates cellular senescence through rDNA instability driven by non-coding RNA transcription.

Identification of Genes Involved in the Degradation of Lignocellulose Using Comparative Transcriptomics.

Lignocellulosic biomass represents an abundant, renewable resource that can be used to produce biofuels, low-cost livestock feed, and high-value chemicals. The potential of this bioresource has led to intensive research efforts to develop cost-effective methods to break down lignocellulose. The efficiency with which the anaerobic fungi (phylum Neocallimastigomycota) degrade plant biomass is well recognized and in recent years has received renewed interest. Transcriptomics has been used to identify enzymes that are expressed by these fungi and are involved in the degradation of a range of lignocellulose feedstocks. The transcriptome is the entire complement of coding and non-coding RNA transcripts that are expressed by a cell under a particular set of conditions. Monitoring changes in gene expression can provide fundamental information about the biology of an organism. Here we outline a general methodology that will enable researchers to conduct comparative transcriptomic studies with the goal of identifying enzymes involved in the degradation of the plant cell wall. The method described will include growth of fungal cultures, isolation and sequencing of RNA, and a basic description of data analysis for bioinformatic identification of differentially expressed transcripts.

LncRNA LENGA acts as a tumor suppressor in gastric cancer through BRD7/TP53 signaling.

It has been established that long noncoding RNAs (lncRNAs) play a crucial role in various cancer types, and there are vast numbers of long noncoding RNA transcripts that have been identified by high-throughput methods. However, the biological function of many novel aberrantly expressed lncRNAs remains poorly elucidated, especially in gastric cancer (GC). Here, we first identified a novel lncRNA termed LENGA (Low Expression Noncoding RNA in Gastric Adenocarcinoma), which was significantly downregulated in GC tissues compared to adjacent normal tissues. Next, we found that reduced expression of LENGA in GC was also associated with a shorter life expectancy. The proliferation, migration, and invasion of GC cells were increased after LENGA knockdown but restrained after LENGA overexpression in vitro and in vivo. It was further demonstrated that LENGA physically binds to BRD7 (bromodomain-containing 7) in the bromodomain domain and acts as a scaffold that enhances the interaction between BRD7 and TP53 (tumor protein p53), regulating the expression of a subset of genes in the p53 pathway, including CDKN1A (cyclin-dependent kinase inhibitor 1A) and PCDH7 (protocadherin 7), at the transcriptional level. Consistently, the expression of CDKN1A has a positive correlation with LENGA in GC patients. Taken together, this study uncovers a novel tumor suppressor lncRNA, LENGA, and describes its biological function, molecular mechanism, and clinical significance. This highlights the potential importance of targeting the LENGA/BRD7/TP53 axis in GC treatment.

Effect of chronic intermittent ethanol vapor exposure on RNA content of brain-derived extracellular vesicles.

Extracellular vesicles (EVs) are important players in normal biological function and disease pathogenesis. Of the many biomolecules packaged into EVs, coding and noncoding RNA transcripts are of particular interest for their ability to significantly alter cellular and molecular processes. Here we investigate how chronic ethanol exposure impacts EV RNA cargo and the functional outcomes of these changes. Following chronic intermittent ethanol (CIE) vapor exposure, EVs were isolated from male and female C57BL/6J mouse brain. Total RNA from EVs was analyzed by lncRNA/mRNA microarray to survey changes in RNA cargo following vapor exposure. Differential expression analysis of microarray data revealed a number of lncRNA and mRNA types differentially expressed in CIE compared to control EVs. Weighted gene co-expression network analysis identified multiple male and female specific modules related to neuroinflammation, cell death, demyelination, and synapse organization. To functionally test these changes, whole-cell voltage-clamp recordings were used to assess synaptic transmission. Incubation of nucleus accumbens brain slices with EVs led to a reduction in spontaneous excitatory postsynaptic current amplitude, although no changes in synaptic transmission were observed between control and CIE EV administration. These results indicate that CIE vapor exposure significantly changes the RNA cargo of brain-derived EVs, which have the ability to impact neuronal function.

Prediction of the cell-type-specific transcription of non-coding RNAs from genome sequences via machine learning.

Gene transcription is regulated through complex mechanisms involving non-coding RNAs (ncRNAs). As the transcription of ncRNAs, especially of enhancer RNAs, is often low and cell type specific, how the levels of RNA transcription depend on genotype remains largely unexplored. Here we report the development and utility of a machine-learning model (MENTR) that reliably links genome sequence and ncRNA expression at the cell type level. Effects on ncRNA transcription predicted by the model were concordant with estimates from published studies in a cell-type-dependent manner, regardless of allele frequency and genetic linkage. Among 41,223 variants from genome-wide association studies, the model identified 7,775 enhancer RNAs and 3,548 long ncRNAs causally associated with complex traits across 348 major human primary cells and tissues, such as rare variants plausibly altering the transcription of enhancer RNAs to influence the risks of Crohn's disease and asthma. The model may aid the discovery of causal variants and the generation of testable hypotheses for biological mechanisms driving complex traits.

Multi-Layered Regulations on the Chromatin Architectures: Establishing the Tight and Specific Responses of Fission Yeast fbp1 Gene Transcription

Transcriptional regulation is pivotal for all living organisms and is required for adequate response to environmental fluctuations and intercellular signaling molecules. For precise regulation of transcription, cells have evolved regulatory systems on the genome architecture, including the chromosome higher-order structure (e.g., chromatin loops), location of transcription factor (TF)-binding sequences, non-coding RNA (ncRNA) transcription, chromatin configuration (e.g., nucleosome positioning and histone modifications), and the topological state of the DNA double helix. To understand how these genome-chromatin architectures and their regulators establish tight and specific responses at the transcription stage, the fission yeast fbp1 gene has been analyzed as a model system for decades. The fission yeast fbp1 gene is tightly repressed in the presence of glucose, and this gene is induced by over three orders of magnitude upon glucose starvation with a cascade of multi-layered regulations on various levels of genome and chromatin architecture. In this review article, we summarize the multi-layered transcriptional regulatory systems revealed by the analysis of the fission yeast fbp1 gene as a model system.

Profiling non-coding RNA expression in cerebrospinal fluid of amyotrophic lateral sclerosis patients

Introduction Objective biomarkers for the fatal neurodegenerative disease amyotrophic lateral sclerosis or motor neuron disease (ALS/MND) are critical for diagnosis, drug development, clinical trials, and insight into disease pathology. Key candidates for biomarkers present in biofluids include non-coding RNA (ncRNA) transcripts including microRNA, piwi-interacting RNA and transfer RNA. To determine if the central nervous system was the source of the dysregulated ncRNA biomarkers we previously observed in serum, we sought to identify dysregulated ncRNA candidates in cerebrospinal fluid (CSF) which may provide new insight into the disease pathology. Methods and materials Small RNA sequencing (RNA-seq) was undertaken on CSF samples from healthy controls (n = 18), disease mimics (n = 8), and ALS patients (n = 40) in our Oxford Study for Biomarkers of ALS cohort, with RT-qPCR used to confirm their dysregulation. Results We found a range of ncRNA that were dysregulated in the RNA-seq screen, but these failed to be validated or detected in some cases using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Additionally, our previously identified serum ncRNA biomarker showed no change in CSF or correlation to serum. Conclusions This study suggests the CSF may not be the source of dysregulated ncRNA in the serum and highlights the difficulty in identifying ncRNA in CSF as biomarkers for ALS. KEY MESSAGES In this current study, we investigated the expression of non-coding RNA transcripts in the cerebrospinal fluid of ALS patients compared to healthy controls. RNA-seq identified dysregulated non-coding RNA transcripts, but these were not validated with RT-qPCR. We conclude that cerebrospinal fluid is not a suitable source of diagnostic biomarkers.

TRNA-derived fragment tRF-1001: A novel anti-angiogenic factor in pathological ocular angiogenesis

Transfer RNA-derived fragments (tRFs) are a novel class of non-coding RNA transcripts and play important roles in several physiological/pathological processes. However, the role of tRFs in ocular angiogenesis remains elusive. Herein, we investigate whether the intervention of tRF-1001 expression could suppress pathological ocular angiogenesis. The results show that the levels of tRF-1001 expression were reduced in the retinas of an oxygen-induced retinopathy (OIR) model, choroidal neovascularization model, and endothelial sprouting model invitro. Increased tRF-1001 expression could suppress ocular angiogenesis and endothelial sprouting invivo and reduce endothelial migration, specification, and sprouting invitro. Mechanistically, tRF-1001 regulated endothelial angiogenic effects via tRF-1001/METTL3/RBPJ-MAML1 signaling. The levels of tRF-1001 expression were downregulated in the aqueous humor of age-related macular degeneration (AMD) patients. tRF-1001 upregulation could suppress AMD aqueous humor-induced endothelial sprouting and pathological angiogenesis. Collectively, tRF-1001 acts as an anti-angiogenic factor during ocular angiogenesis. Targeting tRF-1001-mediated signaling is a therapeutic option for ocular neovascular diseases.

Circular RNAs in diabetes and its complications: Current knowledge and future prospects.

A novel class of non-coding RNA transcripts called circular RNAs (circRNAs) have been the subject of significant recent studies. Accumulating evidence points that circRNAs play an important role in the cellular processes, inflammatory expression, and immune responses through sponging miRNA, binding, or translating in proteins. Studies have found that circRNAs are involved in the physiologic and pathologic processes of diabetes. There has been an increased focus on the relevance of between abnormal circRNA expression and the development and progression of various types of diabetes and diabetes-related diseases. These circRNAs not only serve as promising diagnostic and prognostic molecular biomarkers, but also have important biological roles in islet cells, diabetes, and its complications. In addition, many circRNA signaling pathways have been found to regulate the occurrence and development of diabetes. Here we comprehensively review and discuss recent advances in our understanding of the physiologic function and regulatory mechanisms of circRNAs on pancreatic islet cells, different subtypes in diabetes, and diabetic complications.