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Results for “RNA, Untranslated”

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At least 19 recordsLinked to original sources

PubMed1992

Control of RNase E-mediated RNA degradation by 5'-terminal base pairing in E. coli.

Despite the variety of messenger RNA half-lives in bacteria (0.5-30 min in Escherichia coli) and their importance in controlling gene expression, their molecular basis remains obscure. The lifetime of an entire mRNA molecule can be determined by features near its 5' end, but no 5' exoribonuclease has been identified in any prokaryotic organism. A mutation that inactivates E. coli RNase E also increases the average lifetime of bulk E. coli mRNA and of many individual messages, suggesting that cleavage by this endonuclease may be the rate-determining step in the degradation of most mRNAs in E. coli. We have investigated the substrate preference of RNase E in E. coli by using variants of RNA I, a small untranslated RNA whose swift degradation in vivo is initiated by RNase E cleavage at an internal site. We report here that RNase E has an unprecedented substrate specificity for an endoribonuclease, as it preferentially cleaves RNAs that have several unpaired nucleotides at the 5' end. The sensitivity of RNase E to 5'-terminal base pairing may explain how determinants near the 5' end can control rates of mRNA decay in bacteria.

Bacterial Outer Membrane Proteins↗

PubMed2026

Comparative transcriptome analysis reveals ncRNA-mediated regulatory networks associated with muscle crispiness in grass carp.

Non-coding RNAs (ncRNAs) have been demonstrated to be involved in muscle development and to function as key regulators. However, the molecular mechanism underlying muscle crispiness in grass carp (GC) remains poorly understood, and whether these ncRNAs are involved in its regulation is still unknown. In the current investigation, differentially expressed (DE) RNAs (including lncRNAs, circRNAs, miRNAs, and mRNAs) were identified; concomitantly, target genes prediction was conducted, and functional and signaling pathway enrichment analyses were performed. Pathways related to muscle crispiness were identified, and the competitive endogenous RNA (ceRNA) (lncRNA/circRNA-miRNA-mRNA) regulatory network was further constructed. The results showed that a total of 126 DE-lncRNAs, 17 DE-circRNAs, 329 DE-miRNAs, and 442 DE-mRNAs were identified in muscle tissues of both the GC and crisp grass carp (CGC). GO and KEGG enrichment analyses revealed that target genes of DE-ncRNAs were significantly enriched in signaling pathways, including structural constituents of muscle, apoptosis, oxidative phosphorylation, and regulation of actin cytoskeleton, suggesting that these pathways may be involved in muscle texture remodeling. Subsequently, DE-RNAs enriched in related pathways were identified, and a core ceRNA regulation network comprising 3 lncRNAs, 4 circRNAs, 3 miRNAs, and 17 mRNAs was constructed. Additionally, 10 DE-RNAs from randomly selected groups were validated by qRT-PCR. Our findings not only provide scientific evidence elucidating the molecular mechanisms underlying muscle crispiness in GC but also establish a foundation for studying changes in muscle textural qualities across other fish species.

Animals↗

PubMed2026

Towards efficient perturbation for the noncoding genome.

Deciphering the functionality of the noncoding genome, which includes important cis-regulatory elements (CREs) and transcribed noncoding RNA genes, remains technically challenging. Here, using massively parallel genetic screening, we systematically benchmark the performance of five representative loss-of-function perturbation tools, including single-guide RNA (gRNA) mediated SpCas9 cleavage or CRISPR interference, and paired gRNA (pgRNA) involved dual-SpCas9, Big Papi (paired SpCas9 and SaCas9) or dual-enAsCas12a fragment deletion methods, in decoding the roles of the noncoding genome. For targeting CREs such as enhancers, dual-SpCas9 outperforms other methods with superior efficiency in destroying functional genomic regions. For perturbing noncoding RNA genes, in addition to dual-SpCas9, other RNA-targeting methods such as RNA interference are recommended to discriminate transcript-dependent or -independent roles. A deep learning model, DeepDC, with an associated web server, is built to facilitate optimal dual-SpCas9 pgRNA design for efficiently deleting a genomic fragment. Together, our work provides practical guidance on selecting appropriate loss-of-function tools to resolve the functional complexity of the noncoding genome.

CRISPR-Cas Systems↗

PubMed2026

Non-coding RNA 7SK drives tumor resistance by coupling local oncogenic activation with global transcriptional repression.

The conserved non-coding RNA 7SK is a well-established global transcriptional repressor, yet its context-specific functions in cancer and therapy resistance remain paradoxical. Here, we resolve this paradox by uncovering a dual-axis mechanism through which 7SK drives colorectal cancer (CRC) resistance. By integrating single-cell multi-omics with functional assays, we demonstrate that 7SK not only selectively activates the JUN transcriptional network to fuel tumor proliferation but also reduces global transcriptional entropy to stabilize an immunosuppressive microenvironment and promote immune escape. This "local activation-global suppression" paradigm is conserved across multiple cancer types, positioning 7SK as a potential pan-cancer therapeutic target. Our findings reveal 7SK as a dynamic modulator that balances oncogene-specific transcription with global transcriptional suppression across cancers, providing a new framework for understanding and targeting ncRNA-mediated resistance.

Humans↗

PubMed2025

A Glimpse of Noncoding RNAs: Secondary Structure, Emerging Trends, and Potential Applications in Human Diseases.

An appealing strategy for the treatment of several diseases is the therapeutic targeting of noncoding RNAs (ncRNAs), such as microRNAs (miRNAs) and long noncoding RNAs (lncRNAs). Many antisense oligonucleotides and small interfering RNAs have been tested in clinical studies over the past 10 years, and several of these have received FDA approval. However, trial results have thus far been mixed, with some studies reporting strong effects and others showing low effectiveness or side effects, including toxicity. Clinical trials for alternative entities like antimiRNAs are underway, and interest in lncRNA-based therapies is constantly growing. From this perspective, we discuss the basic overview of ncRNAs, their significant role as therapeutic biomarkers against different diseases, and the role of secondary structure in noncoding RNAs.

Humans↗

PubMed2024

Detection of mitochondrial tDRs in killifish embryos and other non-model organisms.

In recent years a diversity of small noncoding RNAs have been identified that originate from the mitochondrial genome. These mitosRNAs are often dominated by tRNA-derived small RNAs (mito-tDRs). Differential expression of mito-tDRs is associated with responses to stress. They also appear to be expressed differentially during development and their expression may be enriched in stress-tolerant animals. Very little is currently known about roles or modes of action of these sequences, although they are implicated in a diversity of processes such as cell cycle regulation, mRNA stability, regulation of ROS production, and import of proteins into the mitochondrion. To better understand the various roles these sequences may play, it is critical that we understand their diversity, cellular location, and the context for their expression. This protocol outlines the methodologies used to detect mitosRNAs, including mito-tDRs, in embryos and cells of the annual killifish Austrofundulus limnaeus. We highlight critical steps in the isolation of RNA, creation of sequencing libraries, bioinformatics processing of sequence data, and methods for validation of expression that support a robust discovery pipeline for mitosRNAs even from species with incomplete reference genome sequences.

Animals↗

PubMed2025

A hypoxia-responsive tRNA-derived small RNA confers renal protection through RNA autophagy.

Transfer RNA-derived small RNAs (tsRNAs or tDRs) perform a range of cellular functions. Here, we showed that tRNA-Asp-GTC-3'tDR, a hypoxia-induced tDR derived from the 3' end of tRNA-Asp-GTC, activated autophagic flux in kidney cells and its silencing blocked autophagic flux. Functional gain-/loss-of-function studies in murine kidney disease models demonstrated a substantial renoprotective function of tRNA-Asp-GTC-3'tDR. Mechanistically, tRNA-Asp-GTC-3'tDR assembled stable G-quadruplex structures and sequestered pseudouridine synthase 7 (PUS7), preventing catalytic pseudouridylation of histone mRNAs. The resulting pseudouridylation deficiency directed histone mRNAs to the autophagosome-lysosome pathway, triggering RNA autophagy. This tDR-induced RNA autophagy pathway was activated during murine and human kidney diseases, suggesting clinical relevance. Thus, tRNA-Asp-GTC-3'tDR plays a role in regulating RNA autophagy, which helps to maintain homeostasis in kidney cells and protects against kidney injury.

Animals↗

PubMed1975

Nucleotide sequences of the 3'-terminal untranslated region of messenger RNA for human beta globin chain.

In normal messenger RNA for the human beta-globin chain, nucleotide sequences have been identified which can be matched to the amino-acid sequence of the abnormally long segment of the beta-chain of hemoglobin Cranston. The finding of these sequences strengthens the hypothesis that the betaCranston chain arose by a frameshift mutation allowing the "readthrough" of the normal termination codon and translation of usually untranslated portions of the messenger RNA for the beta-globin chain. The oligonucleotides which match the amino-acid sequence of hemoglobin Cranston provide a sequence of 36 nucleotides which follows the normal beta-chain termination codon UAA.

Base Sequence↗

PubMed2026

Hidden proteins encoded by non-canonical open reading frames: A review.

There is increasing evidence that translation is not limited to annotated protein-coding genes. Ribosome profiling sequencing, mass spectrometry-based proteomics, and immunopeptidomics have identified the productive translation of non-canonical open reading frames (ORFs). This suggests that the functional proteome includes not only conserved proteins but also proteins hidden in non-coding RNAs and de novo proteins. Some of these translated products are functional peptides, while others may be non-functional, potentially arising from evolutionary events. Several non-canonical ORF-encoded peptides have been found to regulate multiple physiological and pathological functions, particularly in cancer, immunity, and inflammation, indicating that they have potential as biomarkers and novel therapeutic targets. To better understand the diversity of functional peptides and translated non-canonical ORFs based on existing data, we summarize their classification according to transcriptional features and supporting evidence, including non-canonical ORFs located in ncRNAs and canonical mRNAs. This review provides a concise summary of the origin, discovery methods, and classification of non-canonical ORFs. It offers insights into the origins and functions of non-canonical ORF-encoded peptides from an evolutionary perspective, while also exploring the biological functions and regulatory mechanisms of these non-canonical ORF-encoded hidden proteins in tumorigenesis and progression.

Open Reading Frames↗

PubMed2025

Comparative and systems analyses of Leishmania spp. non-coding RNAs through developmental stages.

Leishmania spp. is the etiological agent of leishmaniases, neglected diseases that seek to be eradicated in the coming years. The life cycle of these parasites involves different host and stress environments. In recent years, many studies have shown that several protein-coding genes are directly involved with the development and host interactions. However, little is still known about the role of non-coding RNAs (ncRNAs) in life cycle progression. In this study, we aimed to identify the genomic structure and function of ncRNAs from Leishmania spp. and to get insights into the repertoire of ncRNAs (RNAome) of this protozoan genus. We studied 26 strains corresponding to 16 different species of Leishmania. Our RNAome analysis revealed the presence of several ncRNAs that are shared among different species, allowing us to differentiate between subgenera as well as between species that are canonically related to visceral leishmaniasis. We also studied co-expression relationships between coding genes and ncRNAs which in the amastigote developmental stage for Leishmania braziliensis and Leishmania donovani revealed the presence of miRNA-like transcripts co-expressed with several coding genes involved in starvation, survival and histone modification. This work represents the first effort to characterize the Leishmania ssp. RNAome, supporting further approaches to better understand the role of ncRNAs in gene regulation, infective process, and host-parasite interaction.

RNA, Untranslated↗

PubMed2026

Non-coding RNAs and Mitochondrial Dysfunction in Alzheimer's Disease: A Systematic Review.

Alzheimer's disease (AD) is responsible for 70% of dementia cases worldwide, with tau hyperphosphorylation and amyloid-β plaque accumulation representing its core pathological hallmarks. Genetic predisposition, oxidative stress, and neuroinflammation contribute to disease onset and progression. Non-coding ribonucleic acids (ncRNAs) are a class of RNAs which control gene expression and whose dysregulation in AD patients has been linked to amyloid production, neuroinflammation, and mitochondrial dysfunction, which ranges from impaired energy metabolism to disrupted mitochondrial biogenesis and dynamics. Our descriptive systematic review surveyed the involvement of ncRNAs in mitochondrial dysfunction in AD across experimental and clinical literature. We identified multiple microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) that directly regulate mitophagy, mitochondrial biogenesis, mitochondrial autophagic, and apoptotic pathways, mitochondrial dynamics, and protein import mechanisms in AD models. Among the most important candidates demonstrating clinical dysregulation, miR-140 and lncRNA NEAT1 regulate mitophagy, while miR-9, miR-34a, miR-146a, miR-155, and miR-485 are implicated in mitochondrial biogenesis and miR-204 in mitochondrial autophagy. LncRNA BDNF-AS, miR-148a-3p, miR-21-5p, and miR-103a-3p emerged as regulators of the mitochondrial apoptosis pathway with confirmed clinical dysregulation. Multiple ncRNAs control mitochondrial dynamics, of which miR-195, miR-124, and miR-455-3p have also been studied in AD patients. Additionally, several ncRNAs were found to indirectly regulate mitochondrial fission, autophagy, and apoptosis, although the underlying mechanisms require further characterization. Thus, while ncRNA-centered AD research is in its early stages, current mechanistic and translational evidence supports mitochondrially relevant ncRNAs as promising candidates for biomarker and therapeutic development.

Alzheimer Disease↗

PubMed2026

Nuclear exosome targeting complexes modulate cohesin binding and enhancer-promoter interactions in 3D.

Three-dimensional long-range contacts between enhancers and promoters are thought to be largely determined by loop extrusion driven by the cohesin complex and insulator factors. However, recent evidence also suggests a role for noncoding RNAs, such as enhancer-associated RNAs and promoter upstream transcripts, in shaping enhancer-promoter connectivity. While the nuclear RNA exosome, together with targeting complexes, poly(A) tail exosome targeting connection and nuclear exosome targeting complex, controls the decay of noncoding RNAs, it remains unclear whether these complexes regulate three-dimensional chromatin contacts. Chromatin recruitment maps of the nuclear exosome targeting complex subunit ZCCHC8, the poly(A) tail exosome targeting connection subunit ZFC3H1, and the RNA helicase MTR4 in human cells reveal that these factors associate with sites of enhancer-promoter interactions. Depletion of these factors leads to the accumulation of ncRNAs, notably enhancer-associated RNAs and promoter upstream transcripts, and increases cohesin occupancy at these sites. Chromatin conformation capture analysis reveals that MTR4 modulates long-range enhancer-promoter contacts. Upon loss of MTR4, enhancer-promoter contacts increase while intraloop contacts decrease, suggesting that MTR4 facilitates loop extrusion. These data highlight a key interplay between cohesin-mediated enhancer-promoter interactions and the regulation of noncoding RNAs by nuclear RNA exosome targeting complexes that is consistent with a role for RNA in genome folding.

Cohesins↗

PubMed2026

Machine learning approaches for cancer prognosis and diagnosis via non-coding RNA: a comprehensive review.

Non-coding RNAs (ncRNAs), once considered genomic dark matter, are now established as key regulators of gene expression with widespread roles in cellular homeostasis and disease. In cancer, ncRNA expression is frequently and systematically dysregulated, and many of these molecules circulate in stable, protected form within biofluids, offering a compelling basis for non-invasive or minimally invasive diagnostic strategies. However, their clinical translation remains substantially hindered to date due to biological complexity, technical noise, and high dimensionality inherent to ncRNA expression datasets. In this context, machine learning (ML) has emerged as a powerful analytical tool to address these challenges, enabling the identification of subtle, reproducible ncRNA signatures predictive of diverse malignancies. This review critically evaluates ML-driven frameworks for cancer diagnosis and prognosis across four ncRNA subclasses, namely miRNAs, lncRNAs, circRNAs, and piRNAs, while also acknowledging the biophysical and thermodynamic models that reinforce ncRNA bioinformatics. Despite substantial methodological progress in ML-based cancer diagnosis and prognosis, key challenges persist, including tumor biological heterogeneity, limited multicenter validation, and the lack of widely adopted standardized protocols for preprocessing, normalization, and reporting workflows. Furthermore, many current ML models lack interpretability in biological or clinical context, constraining their translational utility. By synthesizing recent advances and identifying unresolved barriers, this review charts a roadmap for developing a robust, clinically actionable ncRNA biomarker platform for cancer detection. With global cancer incidence projected to exceed 35 million annual cases by 2050, validated ncRNA-ML-driven frameworks hold potential to revolutionize early-stage detection and personalized therapeutic strategies, thereby reducing the escalating socio-economic burden of cancer worldwide.

Humans↗

PubMed2026

The HOXA gene cluster: a critical regulator in bone-related disorders.

BACKGROUND: Skeletal homeostasis relies on the dynamic balance between bone formation and bone resorption. The disruption of this balance acts as the central pathological mechanism of multiple metabolic bone diseases including osteoporosis, and is closely correlated with the progression of various other bone-related disorders. As pivotal transcription factors regulating embryonic development and cell fate, the homeobox A (HOXA) gene family plays an essential role in skeletal physiological and pathological processes. METHODS: This review systematically summarizes recent research advances of the HOXA gene family in bone-related diseases, concludes the evolutionarily conserved regulatory patterns of HOXA members, and clarifies the molecular mechanisms by which HOXA genes mediate bone metabolic disorders and the occurrence as well as development of bone diseases. RESULTS: Accumulating evidence demonstrates that HOXA family members present complex functions and strong heterogeneity in bone-related diseases. They participate in the pathogenesis of bone diseases via three evolutionarily conserved regulatory manners: determining regional patterning, modulating signaling pathways, and integrating epigenetic and non-coding RNA (ncRNA) regulatory networks. CONCLUSION: Further exploring the underlying mechanisms of the HOXA family in bone-related diseases provides novel insights into the pathogenesis of bone disorders. Meanwhile, it also supplies solid theoretical basis and potential therapeutic targets for the development of novel HOXA-targeted therapeutic strategies against bone diseases.

Humans↗

PubMed1992

Direct detection of circulating hepatitis C virus RNA using probes from the 5' untranslated region.

Diagnostic testing for hepatitis C virus (HCV) infection currently is based on the presence of anti-HCV antibodies or a positive HCV RNA polymerase chain reaction (PCR) test. Although HCV RNA PCR is a sensitive and specific technique, widespread application is limited. Moreover, HCV RNA PCR is subject to false-positive reactions through contamination and is inherently difficult to standardize and quantitate. To overcome limitations of HCV RNA PCR, we produced both cDNA and riboprobes from a 241 nucleotide sequence of the 5' untranslated region of the HCV genome for slot hybridization. Hybridization was absent using normal human serum, horse serum, or hepatic cellular RNA from noninfected liver. Hybridization occurred predominantly with positive-stranded HCV RNA and was abolished by pretreatment with RNase A. Slot hybridization was performed on serum samples from 60 patients with chronic HCV infection and a positive HCV RNA PCR and 20 patients with liver diseases unrelated to HCV who had a negative HCV RNA PCR. Slot hybridization with cDNA and riboprobes showed concordance with HCV RNA PCR of 95 and 98.3%, respectively. There were no false-positive reactions in controls. The sensitivity of riboprobe hybridization was comparable to that of one stage HCV RNA PCR using 5' untranslated region primers. Riboprobe hybridization with the HCV H strain standard was positive in the dilution corresponding to 10(-6) chimpanzee infectious doses50/ml. The density of the hybridization signals correlated significantly with the mass of an RNA standard extracted from the liver of a patient with HCV infection. The relative quantities of HCV RNA in the sera of selected patients varied and were not correlated with the duration of disease or the histopathological stage. The highest relative quantities were associated with concurrent immunosuppression. We conclude that slot hybridization is a sensitive, specific alternative to HCV RNA PCR that can be directly quantitated using appropriate HCV RNA standards.

Base Sequence↗

PubMed2026

The dark genome in cardiovascular medicine.

Only ∼1%-2% of the human genome directly codes for proteins. The remainder consists of non-coding DNA, often referred to as the 'dark genome'. This includes regulatory elements, transposable and repetitive sequences, structural genomic features, pseudogenes, intronic and intergenic regions, and non-coding RNA (ncRNA) genes. These components are increasingly recognized as major regulators of gene expression, cell identity, and disease susceptibility. Currently, dark genome elements, particularly ncRNAs are increasingly recognized as important regulators of cardiovascular health and disease. Advances in genome analysis technologies have greatly improved our understanding of these non-coding regions and revealed clearer connections between the dark genome and cardiovascular traits. This review highlights major parts of the dark genome involved in cardiovascular disease, with emphasis on those for which mechanistic understanding and translational relevance are beginning to emerge. As mechanistic insight into individual and collective components of the dark genome advances, it increasingly enables the development of new opportunities for targeted therapeutics for cardiovascular prevention and disease management.

Humans↗

PubMed2026

A human-specific non-coding RNA for EFHC1, an epilepsy-associated gene, regulates neural stem cell proliferation for cortical development.

Epilepsy is a prevalent brain disorder in humans but rarely occurs naturally in other species, highlighting the potential for human-specific mechanisms in its pathogenesis, and thus, current animal models fail to recapitulate human symptoms. Comparing RNA sequencing (RNA-seq) datasets from human and mouse neural stem cells (NSCs), we identified EFHC1, a juvenile myoclonic epilepsy gene, as exhibiting a human-biased expression. EFHC1 knockdown reduced human NSC proliferation, while its overexpression in mouse embryonic brains increased cortical NSC number. Mechanistically, EFHC1 prevented endoplasmic reticulum stress, thereby reducing inflammatory activation of p38 MAPK and promoting continuous proliferation of human NSCs. We also identified pancEFHC1, a bidirectional promoter-associated non-coding RNA (pancRNA), located at the human EFHC1 promoter. Knockdown of pancEFHC1 in human NSCs increased DNA methylation to reduce EFHC1 expression, with the resulting phenotype rescued by EFHC1 overexpression. We propose that the evolutionary acquisition of pancEFHC1 has introduced a complex regulatory mechanism for EFHC1 expression that allows distinguishing it in humans.

Humans↗

PubMed1992

The 5'-untranslated leader sequence of potato virus X RNA enhances the expression of a heterologous gene in vivo.

The 5' untranslated leader of potato virus X (PVX) RNA is shown when contiguous to the coding sequence, to enhance the expression of the neomycin phosphotransferase II gene (NPTII) in Nicotiana tabacum protoplasts in vivo. The level of transient expression of the NPTII gene in protoplasts provided by a plasmid containing the coding sequence of the NPTII gene under the control of 35S cauliflower mosaic virus (CaMV) promoter and terminator elements served as the baseline control. Insertion of the viral 5' untranslated leader sequence upstream of the NPTII ATG codon increased the level of expression 4-fold. An 83 nucleotide (nt) leader sequence (lacking only one nucleotide of the complete PVX leader) and a truncated version with a 28 deletion at the 3' end both had similar enhancing abilities. The 28 nt CA region of the PVX leader alone had no enhancement properties.

Base Sequence↗