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PubMed2024

Construction of an immunogenic cell death-related LncRNA signature to predict the prognosis of patients with lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is one of the most common malignant diseases worldwide. This study aimed to construct an immunogenic cell death (ICD)-related long non-coding RNA (lncRNA) signature to effectively predict the prognosis of LUAD. METHODS: The RNA-sequencing and clinical data of LUAD were downloaded from The Cancer Genome Atlas (TCGA). Least absolute shrinkage and selection operator (LASSO) and stepwise multivariate Cox proportional hazard regression analysis were utilized to construct lncRNA signature. Then, the reliability of the signature was evaluated in the training, validation and whole cohorts. The differences in the immune landscape and drug sensitivity between the low- and high-risk groups were analyzed. Finally, the expression level of the selected ICD-related lncRNAs in LUAD cell lines via reverse transcription quantitative PCR (RT-qPCR). CCK-8 and transwell assays were performed to study biological function of AC245014.3. RESULTS: A signature consisting of 5 ICD-related lncRNAs was constructed. Kaplan Meier (K-M) survival analysis showed shorter overall survival (OS) in high-risk group. The receiver operating characteristic (ROC) curves and Multivariate Cox regression analysis showed the signature was good predictive and independent prognostic factor in LUAD. Moreover, the high-risk group had a lower level of antitumor immunity and was less sensitive to some chemotherapeutics and targeted drugs. Finally, the expression level of selected ICD-related lncRNAs was validated in LUAD cell lines by RT-qPCR. Knockdown of AC245014.3 significantly suppressed LUAD proliferation, migration and invasion. CONCLUSIONS: In this study, an ICD-related lncRNA signature was constructed, which could accurately predict the prognosis of LUAD patients and guide clinical treatment.

Humans↗

PubMed2025

A targeted CRISPR screen identifies ETS1 as a regulator of HIV-1 latency.

Human Immunodeficiency virus (HIV) infection is regulated by a wide array of host cell factors that combine to influence viral transcription and latency. To understand the complex relationship between the host cell and HIV-1 latency, we performed a lentiviral CRISPR screen that targeted a set of host cell genes whose expression or activity correlates with HIV-1 expression. We further investigated one of the identified factors - the transcription factor ETS1, and found that it is required for maintenance of HIV-1 latency in both latently infected cell lines and in a primary CD4 T cell latency model. Interestingly, ETS1 played divergent roles in actively infected and latently infected CD4 T cells, with knockout of ETS1 leading to reduced HIV-1 expression in actively infected cells, but increased HIV-1 expression in latently infected cells, indicating that ETS1 can play both a positive and negative role in HIV-1 expression. CRISPR/Cas9 knockout of ETS1 in CD4 T cells from ART-suppressed people with HIV-1 (PWH) confirmed that ETS1 maintains transcriptional repression of the clinical HIV-1 reservoir. Transcriptomic profiling of ETS1-depleted cells from PWH identified a set of host cell pathways involved in viral transcription that are controlled by ETS1 in resting CD4 T cells. In particular, we observed that ETS1 knockout increased expression of the long non-coding RNA MALAT1 that has been previously identified as a positive regulator of HIV-1 expression. Furthermore, the impact of ETS1 depletion on HIV-1 expression in latently infected cells was partially dependent on MALAT1. Additionally, we demonstrate that ETS1 knockout resulted in enhanced abundance of activating modifications (H3K9Ac, H3K27Ac, H3K4me3) on histones located at the HIV-1 long terminal repeat (LTR), indicating that ETS1 regulates the activity of chromatin-targeting complexes at the HIV-1 LTR. Overall, these data demonstrate that ETS1 is an important regulator of HIV-1 latency that impacts HIV-1 expression through repressing MALAT1 expression and by regulating modification of proviral histones.

Proto-Oncogene Protein c-ets-1↗

PubMed2026

Mobile elements in pituitary neuroendocrine tumors: integrative evidence and future directions.

Mobile genetic elements (MGEs), including LINE-1 retrotransposons, Alu and SVA elements, and human endogenous retroviruses (HERVs), constitute nearly half of the human genome and are increasingly understood to influence multiple dimensions of cancer evolution. Yet, pituitary neuroendocrine tumors (PitNETs) remain almost absent from mobilome research, despite exhibiting genomic and epigenetic contexts permissive to retroelement activation. In this review, we synthesize current evidence linking MGEs to PitNET biology and delineate unresolved but testable mechanisms. Structural genomic studies demonstrate that Alu-mediated non-allelic homologous recombination contributes to germline mutagenesis in MEN1 and AIP, reinforcing the notion that repetitive DNA architecture shapes PitNET predisposition. Transcriptomic analyses reveal global derepression of transposable elements and LINE-1 hypomethylation in subsets of tumors, while mechanistic connections to chromatin instability emerge from recurrent ATRX/DAXX deficiency and TP53 inactivation, both established repressors of retroelements. Furthermore, the retrocopy-derived long non-coding RNA RPSAP52 exemplifies how mobilome-origin transcripts can be co-opted as oncogenic regulators in PitNETs, acting through HMGA2-dependent proliferative networks. Preliminary data also suggest endogenous retroviral activation, with consistent upregulation of HERV envelope genes across distinct tumor subtypes. Nevertheless, no study has yet systematically mapped somatic mobile-element insertions (MEIs), quantified LINE-1 protein activity, or profiled HERV expression at locus resolution in PitNETs. Mobilome biology represents a tractable and conceptually rich frontier with diagnostic, prognostic, and therapeutic potential in pituitary tumorigenesis.

Humans↗

PubMed2026

lncRNA JPX promotes radioresistance in nasopharyngeal carcinoma via the miR-1301-3p/PIK3R2-mediated autophagy pathway.

BACKGROUND: Nasopharyngeal carcinoma (NPC) represents an aggressive head and neck malignancy with high metastatic potential. Radioresistance remains a major therapeutic obstacle associated with poor prognosis. Although the long non-coding RNA (lncRNA) JPX has been implicated in various cancers, its specific role in NPC radioresistance requires further elucidation. This study aimed to investigate whether JPX modulates radiosensitivity through autophagy regulation and to delineate the underlying molecular mechanisms. METHODS: JPX expression was analyzed in NPC cell lines and The Cancer Genome Atlas (TCGA) datasets, with subcellular localization determined through cellular fractionation. Functional characterization was performed using short hairpin RNA (shRNA)-mediated knockdown in CNE-2 and HONE-1 cell lines. Radiosensitivity was evaluated by clonogenic survival assays at a clinically relevant radiation dose, with cell viability assessed by MTT as a screening measure. while autophagy activity was assessed through Western blot analysis of LC3-II and p62. Molecular interactions were validated using dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. RESULTS: JPX was significantly upregulated in head and neck squamous cell carcinoma (HNSCC) tissues and NPC cell lines, showing predominant cytoplasmic localization. Clinical association analysis in the TCGA-HNSCC cohort revealed that elevated JPX expression correlated with advanced tumor stage and poor overall survival, although NPC-specific clinical validation remains to be established. Genetic silencing of JPX attenuated autophagic flux and enhanced radiosensitivity. Mechanistic investigations revealed that JPX functions as a competitive endogenous RNA (ceRNA) functionally associating with miR-1301-3p, thereby alleviating miR-1301-3p-mediated repression of PIK3R2 and subsequently activating pro-survival autophagy pathways. CONCLUSIONS: The findings demonstrate that JPX promotes radioresistance in NPC through a ceRNA mechanism involving the miR-1301-3p/PIK3R2/autophagy regulatory axis. The JPX/miR-1301-3p/PIK3R2 axis thus emerges as a potential mechanistic candidate for radiosensitization; however, this notion remains strictly provisional and requires rigorous validation in authenticated NPC models, in vivo systems, and patient-derived samples before any translational consideration can be justified. Despite the cell line limitations acknowledged herein, our findings provide a mechanistic framework for understanding JPX-mediated radioresistance that warrants further investigation in more physiologically relevant models.

JPX↗

PubMed2026

Genomic and epigenomic diversity of breast cancer across Western and MENA populations: implications for precision oncology.

Breast cancer is the most common malignancy in women worldwide and is increasingly recognized as a biologically diverse disease shaped by both molecular and ancestral context. Women from the Middle East and North Africa (MENA) populations, including Saudi Arabia, often present at a younger age and with more aggressive subtypes such as HER2-positive and triple-negative breast cancer (TNBC) compared with Western cohorts. These clinical patterns reflect a distinctive genomic background marked by high consanguinity, founder mutations in key susceptibility genes, and population-specific somatic alterations that are not fully captured in global reference datasets. This review brings together current evidence on somatic, germline, transcriptomic, and epigenomic diversity in breast cancer across Western and MENA populations, with a focus on Saudi cohorts. Drawing on a previously published systematic review of more than 2,500 MENA breast cancer cases, TP53 accounted for approximately 24% and PIK3CA for roughly 10% of curated somatic mutation records pooled across 44 studies (proportions of mutation calls, not per-patient prevalence); in a separate single-center Saudi cohort, only 3.7% of patients underwent BRCA testing, and 37.5% of this clinically selected, testing-referred subgroup carried a pathogenic variant, a figure that should not be read as general-population BRCA prevalence. Variants of uncertain significance exceeded 20% across several regional genomic studies. We summarize conserved driver events, such as recurrent TP53 and PIK3CA mutations, while highlighting regional features, including unique stop-gain and loss-of-function variants, a high copy-number burden, and early-onset disease linked to ancestral architecture. We also discuss emerging data on MENA-specific regulatory signatures, including immune-enriched and basal-myo transcriptomic clusters, CIMP-like methylation patterns, and non-coding RNA networks; these associations are numerically suggestive in available cohorts but have not reached statistical significance in existing studies and warrant validation in larger, dedicated MENA/Saudi cohorts before being considered established determinants of treatment response and resistance. Finally, we examine the clinical implications of this diversity for biomarker development, pharmacogenomics, and access to targeted therapies, and outline practical steps toward ancestry-aware precision oncology in the region.

BRCA↗

PubMed2026

How advances in machine learning drive early detection and risk prediction of early-onset colorectal cancer.

Early-onset colorectal cancer (EOCRC), defined as colorectal cancer diagnosed before age 50, is rising across high- and middle-income settings whilst organised screening stays anchored to older age thresholds. Blood-based liquid biopsy, combined with machine learning, is the most plausible route to early detection in this group because it does not depend on bowel preparation, endoscopy capacity, or adherence to stool-based testing. The gap is structural: incidence climbs fastest in the population below the age at which any guideline-endorsed modality is offered. The analytical challenge is that early-stage tumour-derived signals in plasma are low in abundance and distributed across heterogeneous molecular layers: circulating tumour DNA mutations, aberrant methylation, cfDNA fragmentomics, and small non-coding RNA. Machine learning converts these into a single calibrated probability. This review examines where artificial intelligence (AI)-driven liquid biopsy genuinely adds diagnostic value in EOCRC, distinguishes components in which learned models are decorative from those in which they are mechanistically necessary, and identifies the validation deficit separating research cohorts from deployable clinical tools. It summarises the first-generation tools used clinically for early detection and post-treatment monitoring, then considers analytes from exosome-bound microRNAs to long-read whole-genome sequencing of circulating plasma DNA, which reads cytosine modification natively, resolves methylation and fragmentation on single molecules, and characterises structural events short reads cannot anchor. Any analyte can feed a learned model, but more diverse input yields better discrimination. The central argument is that approved, guideline-included blood tests were validated in populations aged 45 and above, and their performance in younger patients cannot be assumed.

cfDNA fragmentomics↗

PubMed2026

LncRNA RP11-708J19.2 promotes colorectal cancer progression by binding to SIRT7 via regulating H3K18ac.

Colorectal cancer (CRC) is a prevalent malignancy with a complex genetic basis. Recent genome-wide association studies (GWAS) have identified a susceptibility locus at 3p21.31, however, the functional SNP(s) underlying the association between the 3p21.31 region and CRC remain to be elucidated. In this study, we identified rs2101247 as the potential functional SNP and further demonstrated that rs2101247 is significantly associated with the expression of the nearby long non-coding RNA (lncRNA) RP11-708J19.2 (ENSG00000271161.1). Functional experiments showed that RP11-708J19.2 is upregulated in CRC tumor tissues, and its knockdown reduces cell viability while promoting apoptosis in SW1116 and HCT116 cell lines. Mechanistically, RP11-708J19.2 interacts directly with the deacetylase SIRT7, modulating histone H3K18 acetylation (H3K18ac). Specifically, RP11-708J19.2 knockdown leads to a significant upregulation of H3K18ac levels, implicating a SIRT7-mediated epigenetic pathway in CRC progression. Our findings elucidate a novel functional SNP-lncRNA axis that contributes to CRC pathogenesis, providing potential biomarkers for early detection and therapeutic targets for intervention.

Humans↗

PubMed1992

Poa semilatent virus, a hordeivirus having no internal polydisperse poly(A) in the 3' non-coding region of the RNA genome.

RNA from the Hungarian isolate of poa semilatent virus (PSLV) directed in vitro synthesis of 120K, 75K, 25K (coat protein) and 20K polypeptides. In vitro translation of PSLV RNA was blocked by the cap analogue, m7Gpp, thus suggesting that the virus RNA was capped. PSLV RNA could be aminoacylated with [14C]tyrosine in vitro. The sequence of 1.5 kb from the 3' end of the PSLV RNA gamma component revealed two open reading frames (ORFs) separated by a uridine-rich intergenic region. The putative product of the incomplete 5'-proximal ORF showed a close amino acid sequence similarity with the C-terminal segment of the gamma a protein (putative RNA replicase) encoded in the barley stripe mosaic virus (BSMV) RNA gamma, and the 20K product of the 3'-proximal ORF was found to be related to the 17K gamma b product of BSMV. The sequence of 0.8 kb from the 3' end of PSLV RNA beta encompassed two (incomplete) overlapping ORFs whose putative products are related to the beta c and beta d proteins encoded in the similarly arranged ORFs of BSMV RNA beta. Nucleotide sequence homology between the respective parts of the two hordeivirus genomes was restricted to the ORF for gamma a, the spacer between the ORFs for gamma a and gamma b, and the 3' non-coding region, particularly the 95 nucleotide segment at the 3' end representing a tRNA-like structure. Despite limited sequence conservation beyond this segment, the entire 3' non-coding region of PSLV RNA could be folded in a tight pseudoknotted structure closely resembling that of BSMV RNA. Surprisingly, the 'signature' sequence typical for BSMV RNA, internal polydisperse poly(A) intercalated between the coding part of the 3' tRNA-like structure, was not detected in the PSLV genome. Instead, the virus RNA contained several oligoadenylate stretches spaced by other residues, close to the junction of its coding and 3' non-coding portions.

Amino Acid Sequence↗

PubMed1990

The 5'-terminal non-coding region of Murray Valley encephalitis virus RNA is highly conserved.

The 5' non-coding region of the genomes of 11 isolates of Murray Valley encephalitis virus from Australia and Papua New Guinea were examined by primer extension sequencing. Although the 5' non-coding region of all isolates was found to be highly conserved, three isolates were significantly different in that they contained extra uridine residues. Two of these isolates from Papua New Guinea contained an extra uridine residue, nominally positioned after nucleotide 54, which was absent from all but one of the Australian isolates tested. This isolate (OR 156) contained a further uridine residue at the same site. These results provide further support for earlier observations on the genetic relationships between these isolates, in particular that OR 156 is more closely related to the Papua New Guinea strains than to the Australian strains.

Animals↗

PubMed2024

Whole transcriptome sequencing analyses of islets reveal ncRNA regulatory networks underlying impaired insulin secretion and increased β-cell mass in high fat diet-induced diabetes mellitus.

AIM: Our study aims to identify novel non-coding RNA-mRNA regulatory networks associated with β-cell dysfunction and compensatory responses in obesity-related diabetes. METHODS: Glucose metabolism, islet architecture and secretion, and insulin sensitivity were characterized in C57BL/6J mice fed on a 60% high-fat diet (HFD) or control for 24 weeks. Islets were isolated for whole transcriptome sequencing to identify differentially expressed (DE) mRNAs, miRNAs, IncRNAs, and circRNAs. Regulatory networks involving miRNA-mRNA, lncRNA-mRNA, and lncRNA-miRNA-mRNA were constructed and functions were assessed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. RESULTS: Despite compensatory hyperinsulinemia and a significant increase in β-cell mass with a slow rate of proliferation, HFD mice exhibited impaired glucose tolerance. In isolated islets, insulin secretion in response to glucose and palmitic acid deteriorated after 24 weeks of HFD. Whole transcriptomic sequencing identified a total of 1324 DE mRNAs, 14 DE miRNAs, 179 DE lncRNAs, and 680 DE circRNAs. Our transcriptomic dataset unveiled several core regulatory axes involved in the impaired insulin secretion in HFD mice, such as miR-6948-5p/Cacna1c, miR-6964-3p/Cacna1b, miR-3572-5p/Hk2, miR-3572-5p/Cckar and miR-677-5p/Camk2d. Additionally, proliferative and apoptotic targets, including miR-216a-3p/FKBP5, miR-670-3p/Foxo3, miR-677-5p/RIPK1, miR-802-3p/Smad2 and ENSMUST00000176781/Caspase9 possibly contribute to the increased β-cell mass in HFD islets. Furthermore, competing endogenous RNAs (ceRNA) regulatory network involving 7 DE miRNAs, 15 DE lncRNAs and 38 DE mRNAs might also participate in the development of HFD-induced diabetes. CONCLUSIONS: The comprehensive whole transcriptomic sequencing revealed novel non-coding RNA-mRNA regulatory networks associated with impaired insulin secretion and increased β-cell mass in obesity-related diabetes.

Mice↗

PubMed2026

EGFR-co-amplified lncRNA ELDR drives glioblastoma tumorigenicity by enhancing BMI1 activity.

BACKGROUND: In glioblastoma (GBM), epidermal growth factor receptor (EGFR) amplification, one of the most prevalent genetic alterations, often occurs on extrachromosomal DNAs (ecDNAs) that contain amplified oncogenes and regulatory elements, driving tumor progression. Despite the central oncogenic role of EGFR amplification, therapeutic strategies targeting EGFR have demonstrated limited clinical efficacy, suggesting that additional mechanisms may underlie EGFR-driven GBM malignancy and treatment resistance. Long non-coding RNAs (lncRNAs) are critical regulators in cancer; however, the roles of EGFR-associated lncRNAs-particularly those localized on ecDNA-in GBM tumorigenicity and therapeutic resistance remain poorly understood. METHODS: Transcriptomic and genomic analyses were performed to identify lncRNAs co-amplified with EGFR. Biochemical and molecular biological studies were carried out to reveal the mechanisms. In vivo xenograft models were used to evaluate the tumorigenicity and the therapeutic efficacy of combination treatment strategies. RESULTS: The lncRNA EGFR long non-coding downstream RNA (ELDR) was co-amplified with EGFR on ecDNA and chromosomes and was associated with poor prognosis in glioma. ELDR promoted GBM tumorigenicity through a BMI1-dependent epigenetic mechanism operating in parallel with canonical EGFR signaling. Mechanistically, ELDR interacted with purine-rich element-binding protein A (PURA), disrupted the inhibitory PURA-BMI1 interaction, and thereby enhanced the activity of BMI1, a core component of Polycomb repressive complex 1 (PRC1). Therapeutically, combining a BMI1 inhibitor or ELDR-targeting antisense oligonucleotides (ASOs) with an EGFR inhibitor erlotinib significantly enhanced antitumor efficacy in preclinical models of  EGFR  -amplified GBM with high ELDR expression. CONCLUSION: EGFR co-amplified ELDR promotes GBM tumorigenicity by enhancing BMI1 activity. Targeting the ELDR-BMI1 axis in combination with EGFR inhibition represents a promising therapeutic strategy for a subset of  EGFR  -amplified GBMs with high ELDR expression.

EGFR↗

PubMed1989

Sequences in the 5' non-coding region of human rhinovirus 14 RNA that affect in vitro translation.

A subgenomic cDNA clone from human rhinovirus 14 (HRV-14), comprising the 5' non-coding region and the first 1182 nucleotides of the coding sequence, has been inserted into a vector under the control of the T7 promoter, and RNA was transcribed. Deletions in the 5' non-coding sequence modulated viral polyprotein synthesis significantly in a reticulocyte lysate system. Removal of the first 491 nucleotides had little effect, but deletion of a further 55 nucleotides (491 to 546) significantly increased the efficiency of the translation process. Further deletion to nucleotide 621 almost abolished translation, suggesting an essential role for the 546 to 621 nucleotide sequence. The efficiency of the translation process can also be influenced by the addition of ribosomal salt wash prepared from uninfected HeLa cells.

DNA↗

PubMed1988

Nucleotide sequence of the capsid protein gene and 3' non-coding region of papaya mosaic virus RNA.

The nucleotide sequences of cDNA clones corresponding to the 3' OH end of papaya mosaic virus RNA have been determined. The 3'-terminal sequence obtained was 900 nucleotides in length, excluding the poly(A) tail, and contained an open reading frame capable of giving rise to a protein of 214 amino acid residues with an Mr of 22930. This protein was identified as the viral capsid protein. The 3' non-coding region of PMV genome RNA was about 121 nucleotides long [excluding the poly(A) tail] and homologous to the complementary sequence of the non-coding region at the 5' end of PMV RNA. A long open reading frame was also found in the predicted 5' end region of the negative strand.

Amino Acid Sequence↗

PubMed2026

Context-dependent effects of MIR100HG on tumorigenic phenotypes and p38/MAPK-AKT signaling in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide and is characterized by a hypoxic tumor microenvironment that promotes tumor progression, cellular adaptation, and therapeutic resistance. Increasing evidence indicates that long non-coding RNAs (lncRNAs) play critical roles in regulating tumor-associated signaling networks; however, the contribution of MIR100HG to hepatocellular carcinoma progression, particularly under hypoxic conditions, remains insufficiently understood. In this study, we investigated the expression pattern and functional significance of MIR100HG in hepatocellular carcinoma using epithelial-like Hep3B and mesenchymal-like SNU-398 cells, together with non-tumor hepatocytes (Clone-9). Gain- and loss-of-function approaches were employed to evaluate the impact of MIR100HG on tumor-associated cellular phenotypes under both normoxic and hypoxic conditions. Functional assays demonstrated that MIR100HG overexpression significantly enhanced cell proliferation, clonogenic potential, migration, and invasion, whereas MIR100HG silencing markedly suppressed these tumorigenic properties and increased apoptotic cell death. Mechanistic analyses revealed that MIR100HG promotes oncogenic signaling through the p38/MAPK and AKT pathways under normoxic conditions, whereas MIR100HG depletion reduced the phosphorylation of these key signaling proteins. Notably, additional pathway analyses under hypoxia-mimicking conditions revealed a distinct signaling response, in which the MIR100HG-associated activation of p38/MAPK and AKT observed under normoxia was not maintained. Moreover, the expression patterns of AKT-associated regulatory genes, including GAS6 and PTEN, were reversed under hypoxia-mimicking conditions. These findings suggest that the effects of MIR100HG on oncogenic signaling are highly dependent on the cellular oxygenation context and that hypoxia reshapes the downstream signaling consequences of MIR100HG expression in HCC cells. Collectively, our findings identify MIR100HG as a hypoxia-associated oncogenic regulator that enhances tumorigenic phenotypes and promotes survival signaling in hepatocellular carcinoma. These results highlight MIR100HG as a potential biomarker and therapeutic target in liver cancer and provide new insights into the molecular mechanisms underlying hypoxia-driven tumor progression.

Humans↗

PubMed1989

Nucleotide sequences of 5' and 3' non-coding regions of pepper mild mottle virus strain S RNA.

The nucleotide sequences of the 5' and 3' non-coding regions of pepper mild mottle virus strain S (PMMV-S) RNA were determined; they are more like corresponding sequences of tomato mosaic virus (ToMV) RNA than those of any other tobamovirus reported so far. The 5' leader contains a 68 nucleotide guanosine-free sequence which differs in several nucleotides from the corresponding sequences in genomic RNA of tobacco mosaic virus (TMV) and ToMV. The messenger activity of PMMV-S RNA in vitro and the polypeptide translation products made were similar to those of TMV RNA. It therefore seems unlikely that qualitative or quantitative differences in translation in vivo account for the milder symptoms induced by PMMV-S, and its lesser replication, than TMV. The 3' non-coding region of PMMV-S RNA is 199 nucleotides long and can be folded into the same secondary structure as the RNA of other tobamoviruses.

Base Sequence↗

PubMed1984

Screening recombinant phage M13 plaques with RNA probes; a one-step procedure which identifies clones containing either of the complementary DNA strands.

We describe a method for detecting specific DNA sequences cloned in M13 phage vectors, based on the procedure of Woo (in Wu, R., Methods in Enzymology, Vol. 68, Academic Press, New York, 1979, pp. 389-395). M13 plaques are adsorbed to a nitrocellulose filter that has been pre-saturated with bacteria. The filter is incubated on an agar plate to amplify the phage; the DNA is alkali-denatured and then hybridized with a radioactive RNA probe. Unlike standard procedures, this method detects and distinguishes M13 plaques containing phage particles which harbor either the coding or non-coding (RNA-like) DNA strand, when single-stranded RNA is used as probe. We have optimized this procedure with M13 clones containing mouse histidine tRNA gene sequences and have used it to determine the sequence of both strands of a mouse glycine tRNA gene.

Animals↗

PubMed2017

Future of rAAV Gene Therapy: Platform for RNAi, Gene Editing, and Beyond.

The use of recombinant adeno-associated viruses (rAAVs) ushered in a new millennium of gene transfer for therapeutic treatment of a number of conditions, including congenital blindness, hemophilia, and spinal muscular atrophy. rAAV vectors have remarkable staying power from a therapeutic standpoint, withstanding several ebbs and flows. As new technologies such as clustered regularly interspaced short palindromic repeat genome editing emerge, it is now the delivery tool-the AAV vector-that is the stalwart. The long-standing safety of this vector in a multitude of clinical settings makes rAAV a selling point in the advancement of approaches for gene replacement, gene knockdown, gene editing, and genome modification/engineering. The research community is building on these advances to develop more tailored delivery approaches and to tweak the genome in new and unique ways. Intertwining these approaches with newly engineered rAAV vectors is greatly expanding the available tools to manipulate gene expression with a therapeutic intent.

Dependovirus↗

PubMed2026

RNA splicing and cardiovascular disease: a guide for cardiologists.

Alternative splicing (AS) is a fundamental RNA processing mechanism, which generates different RNA transcripts and consequently different protein isoforms from a single gene. This increases the diversity of proteins within an organism and can fine-tune biological processes. This review examines how cardiac-enriched RNA-binding proteins establish heart-specific splicing programs governing aspects of cardiac development, function, and disease. Developmentally, coordinated sarcomeric isoform switches underpin the foetal-to-adult transition and further isoform rewiring in ion channel and kinase genes determine electrophysiology and excitation-contraction coupling. AS contributes to the pathogenesis of several cardiomyopathies and emerging datasets suggest that pathological hypertrophy engages distinct splicing signatures compared with physiological hypertrophy. This review summarizes diagnostic and prognostic opportunities arising from bulk, long-read, and single-cell/nucleus transcriptomics, which resolve cell type-specific isoforms and disease-associated switches. Circulating RNA biomarkers (including splice ratios and circularRNAs) may signify myocardial remodelling and arrhythmic risk. Integrative approaches that link AS with proteomics and genomics improve variant interpretation, reveal previously unannotated protein isoforms, and enable tracking of disease progression and therapy response. Finally, an outline of therapeutic strategies to modulate AS in cardiovascular disease (CVD), including antisense oligonucleotides, small molecules, and genome-editing modalities (CRISPR, base, and prime editing), is provided. The major challenges that remain before splice-targeting therapeutics can be targeted to treat cardiovascular disease are highlighted. Lessons from neuromuscular indications establish clinical feasibility of splicing correction and motivate translation to cardiology. Together, mechanistic insight, biomarker development, and therapeutic innovation position RNA splicing as a tractable axis for precision cardiovascular medicine.

Humans↗