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Results for “noncoding RNA”

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PubMed1991

A complex RNA sequence determines the internal initiation of encephalomyocarditis virus RNA translation.

Translation initiation on EMCV RNA occurs via binding of ribosomes to an internal sequence within the 5' noncoding region. To investigate the organization of the internal ribosome entry site (IRES) we have determined the translational efficiencies of a series of deletion mutants within the 5' noncoding region of EMCV RNA. Three functional regions have been distinguished: a sequence between nts 315-484 and the upper parts of the double-helical structural domains III (nts 488-647) and IV (nts 701-763). The first one greatly enhances translation, but is not absolutely necessary for internal initiation. The other two regions are indispensable to this process. A sequence within domain IV determines inhibition of in vitro translation of mRNAs with 5'-terminal dependent initiation. It is proposed to interact with a translational factor(s) common to the internal and 5'-terminal dependent initiation.

Binding Sites↗

PubMed2000

CD8 coreceptor extinction in signaled CD4(+)CD8(+) thymocytes: coordinate roles for both transcriptional and posttranscriptional regulatory mechanisms in developing thymocytes.

T-cell development in the thymus is characterized by changing expression patterns of CD4 and CD8 coreceptor molecules and by changes in CD4 and CD8 gene transcription. In response to T-cell receptor (TCR) signals, thymocytes progress through developmental transitions, such as conversion of CD4(+)CD8(+) (double-positive [DP]) thymocytes into intermediate CD4(+)CD8(-) thymocytes, that appear to require more-rapid changes in coreceptor expression than can be accomplished by transcriptional regulation alone. Consequently, we considered the possibility that TCR stimulation of DP thymocytes not only affects coreceptor gene transcription but also affects coreceptor RNA stability. Indeed, we found that TCR signals in DP thymocytes rapidly destabilized preexisting CD4 and CD8 coreceptor RNAs, resulting in their rapid elimination. Destabilization of coreceptor RNA was shown for CD8alpha to be dependent on target sequences in the noncoding region of the RNA. TCR signals also differentially affected coreceptor gene transcription in DP thymocytes, terminating CD8alpha gene transcription but only transiently reducing CD4 gene transcription. Thus, posttranscriptional and transcriptional regulatory mechanisms act coordinately in signaled DP thymocytes to promote the rapid conversion of these cells into intermediate CD4(+)CD8(-) thymocytes. We suggest that destabilization of preexisting coreceptor RNAs is a mechanism by which coreceptor expression in developing thymocytes is rapidly altered at critical points in the differentiation of these cells.

Animals↗

PubMed2004

On the role of RNA silencing in the pathogenicity and evolution of viroids and viral satellites.

Viroids and most viral satellites have small, noncoding, and highly structured RNA genomes. How they cause disease symptoms without encoding proteins and why they have characteristic secondary structures are two longstanding questions. Recent studies have shown that both viroids and satellites are capable of inducing RNA silencing, suggesting a possible role of this mechanism in the pathology and evolution of these subviral RNAs. Here we show that preventing RNA silencing in tobacco, using a silencing suppressor, greatly reduces the symptoms caused by the Y satellite of cucumber mosaic virus. Furthermore, tomato plants expressing hairpin RNA, derived from potato spindle tuber viroid, developed symptoms similar to those of potato spindle tuber viroid infection. These results provide evidence suggesting that viroids and satellites cause disease symptoms by directing RNA silencing against physiologically important host genes. We also show that viroid and satellite RNAs are significantly resistant to RNA silencing-mediated degradation, suggesting that RNA silencing is an important selection pressure shaping the evolution of the secondary structures of these pathogens.

Base Sequence↗

PubMed1981

In vivo transcription of the 5'-terminal extracistronic region of vesicular stomatitis virus RNA.

In vivo transcription and polyadenylation at the junction of the L cistron and the 5'-terminal extracistronic region of vesicular stomatitis virus RNA was investigated. Annealing of 5'32P-labeled RNA representing the 5'-terminal noncoding 77 nucleotides of vesicular stomatitis virus genomic RNA to L gene mRNA resulted in specific duplex formation. Two specific RNase T1- and RNase A resistant duplexes, 66 and 77 nucleotides long, bound to oligodeoxythymidylic acid cellulose. The specific sizes of the duplexes and their selection by oligodeoxythymidylic acid cellulose chromatography demonstrated that they were covalently linked to the polyadenylic acid tail of L gene mRNA. These data strongly suggest that the viral polymerase polyadenylates L gene mRNA in vivo by using the stretch of seven uridine residues at the end of the L cistron and that the polymerase can resume transcribing the 5'-terminal extracistronic region, resulting in a covalent linkage of the transcript to the polyadenylic acid tail of L gene mRNA.

Genes↗

PubMed2024

RNA-seq reveals differentially expressed lncRNAs and circRNAs and their associated functional network in HTR-8/Svneo cells under hypoxic conditions.

Placental hypoxia is hazardous to maternal health as well as fetal growth and development. Preeclampsia and intrauterine growth restriction are common pregnancy problems, and one of the causes is placental hypoxia. Placental hypoxia is linked to a number of pregnancy illnessesv. To investigate their potential function in anoxic circumstances, we mimicked the anoxic environment of HTR-8/Svneo cells and performed lncRNA and circRNA studies on anoxic HTR-8/Svneo cells using high-throughput RNA sequencing. The miRNA target genes were predicted by integrating the aberrant expression of miRNAs in the placenta of preeclampsia and intrauterine growth restriction, and a ceRNA network map was developed to conduct a complete transcriptomic and bioinformatics investigation of circRNAs and lncRNAs. The signaling pathways in which the genes were primarily engaged were predicted using GO and KEGG analyses. To propose a novel explanation for trophoblastic organism failure caused by lncRNAs and circRNAs in an anoxic environment.

Humans↗

PubMed1990

A region of the 5' noncoding region of foot-and-mouth disease virus RNA directs efficient internal initiation of protein synthesis within cells: involvement with the role of L protease in translational control.

Plasmids encoding bicistronic mRNAs have been constructed and used to identify a region from the 5' noncoding region of foot-and-mouth disease virus (FMDV) which directs efficient internal initiation of protein synthesis within cells. The loss of about 30 nucleotides (nt) from the 5' terminus or about 50 nt from the 3' terminus of the 435-nt region completely abolished the activity of this region. The expression of the FMDV L protease severely inhibited the expression of other genes unless they were preceded by this element. The regulation of protein synthesis mediated by FMDV is discussed.

Animals↗

PubMed2005

A Kaposi's sarcoma virus RNA element that increases the nuclear abundance of intronless transcripts.

The Kaposi's sarcoma-associated herpesvirus produces a 1077 nucleotide noncoding, polyadenylated, exclusively nuclear RNA called PAN that is highly expressed in lytically infected cells. We report that PAN contains a novel post-transcriptional element essential for its abundant accumulation. The element, PAN-ENE (PAN RNA expression and nuclear retention element), increases the efficiency of 3'-end formation in vivo and is sufficient to enhance RNA abundance from an otherwise inefficiently expressed intronless beta-globin construct. The PAN-ENE does not concomitantly increase the production of encoded protein. Rather, it retains the unspliced beta-globin mRNA in the nucleus. Tethering of export factors can override the nuclear retention of the PAN-ENE, supporting a mechanism whereby the PAN-ENE blocks assembly of an export-competent mRNP. The activities of the PAN-ENE are specific to intronless constructs, since inserting the PAN-ENE into a spliced beta-globin construct has no effect on mRNA abundance and does not affect localization. This is the first characterization of a cis-acting element that increases RNA abundance of intronless transcripts but inhibits assembly of an export-competent mRNP.

Base Sequence↗

PubMed1993

Identification of the hepatitis A virus internal ribosome entry site: in vivo and in vitro analysis of bicistronic RNAs containing the HAV 5' noncoding region.

Hepatitis A virus (HAV), a RNA virus of positive polarity, contains a long 5' noncoding region (5'NCR) that lacks the characteristic m7GpppN cap group of most eukaryotic messages. By creating bicistronic constructs that contain the bacterial chloramphenicol acetyltransferase gene followed by the HAV 5'NCR and the luciferase gene we have demonstrated by assaying in vitro and in vivo that ribosome entry for translation initiation occurs via binding to sequences within the HAV 5'NCR. Using mutations created within this region we have identified that the HAV internal ribosome entry site (IRES) is located downstream of nucleotide 45 and including sequences up to nucleotide 734 of the HAV 5'NCR. Translation of a number of mutant constructs both in vitro in a rabbit reticulocyte lysate and in vivo by transfection of the cDNAs into BS-C-1 cells in the presence of the recombinant vaccinia virus, vTF7-3, gave similar results. However, a 4-nucleotide insertion at base 628 showed an increased activity over wild-type when transfected into BS-C-1 cells that was not seen in vitro. This increase in activity correlated with an increase in luciferase gene product as assayed by immunoprecipitations of [35S]methionine radiolabeled cells. Comparison of mono- and bicistronic RNAs that were synthesized with or without a m7GpppG cap group showed a competition for ribosome binding when translated in a rabbit reticulocyte lysate system. The presence of the cap group on the RNA 5'terminus of the RNA led to a greater ability of this RNA to translate than the RNA containing the HAV IRES.

Animals↗

PubMed2004

Tsix transcription- versus RNA-based mechanisms in Xist repression and epigenetic choice.

Recent inquiries have revealed a surprisingly large number (>2500) of naturally occurring antisense transcripts, but their function remains largely undiscovered. A better understanding of antisense mechanisms is clearly needed because of their potentially diverse roles in gene regulation and disease. A well-documented case occurs in X inactivation, the mechanism by which X-linked gene expression is equalized between XX females and XY males. The antisense gene Tsix determines X chromosome choice and represses the noncoding silencer, Xist. In principle, Tsix action may involve RNA, the act of transcription, or local chromatin. Here, we create novel Tsix alleles to distinguish transcription- versus RNA-based mechanisms. When Tsix transcription is terminated before Xist (TsixTRAP), Tsix cannot block Xist upregulation, suggesting the importance of overlapping antisense transcription. To separate the act of transcription from RNA, we knocked in Tsix cDNA in the reverse orientation (Tsix(cDNA)) to restore RNA levels in cis without concurrent transcription across Xist. However, Tsix(cDNA) cannot complement TsixTRAP. Surprisingly, both mutations disrupt choice, indicating that this epigenetic step requires transcription. We conclude that the processed antisense RNA does not act alone and that Tsix function specifically requires antiparallel transcription through Xist. A mechanism of transcription-based feedback regulation is proposed.

Cells, Cultured↗

PubMed2002

Kissing interaction between 3' noncoding and coding sequences is essential for porcine arterivirus RNA replication.

We used an infectious cDNA clone of porcine reproductive and respiratory syndrome virus (PRRSV) to investigate the presence of essential replication elements in the region of the genome encoding the structural proteins. Deletion analysis showed that a stretch of 34 nucleotides (14653 to 14686) within ORF7, which encodes the nucleocapsid protein, is essential for RNA replication. Strand-specific reverse transcription-PCR analysis of viral RNA isolated from transfected BHK-21 cells revealed that this region is required for negative-strand genomic RNA synthesis. The 34-nucleotide stretch is highly conserved among PRRSV isolates and folds into a putative hairpin. A 7-base sequence within the loop of this structure was suggested to base-pair with a sequence present in the loop of a hairpin located in the 3' noncoding region, resulting in a kissing interaction. Mutational analyses confirmed that this kissing interaction is required for RNA replication.

3' Untranslated Regions↗

PubMed1990

Substitutions in the protease (3Cpro) gene of poliovirus can suppress a mutation in the 5' noncoding region.

The poliovirus mutant 5NC-11 has a 4-base insertion at position 70 within the 5' untranslated region and is deficient in RNA synthesis. Revertants from 5NC-11 were isolated, showing a partial recovery of wild-type levels of RNA synthesis. The 5' noncoding region of those revertants contained the mutation intact; mix-and-match experiments with the cDNA from these revertants revealed that a restricted region within the 3C gene was the site of the suppressing mutations in the revertants. The suppressors were point mutations, confirmed by introducing them into the 3C gene by site-directed mutagenesis. Although complementation studies indicated that the suppressors were cis active, we believe that protein changes rather than RNA sequence alterations are responsible for the suppression because RNA changes that did not alter protein sequence had no effect, whereas various protein alterations were suppressive. The results therefore imply that protein 3C interacts with the 5' end of the RNA and may play a role in RNA replication.

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↗

PubMed2025

Genome imbalance modulates the expression of long non-coding RNAs in maize.

Genome imbalance, resulting from varying the dosage of individual chromosomes (aneuploidy), has a more detrimental effect than changes in complete sets of chromosomes (haploidy/polyploidy). This imbalance is likely due to disruptions in stoichiometry and interactions among macromolecular assemblies. Previous research has shown that aneuploidy causes global modulation of protein-coding genes (PCGs), microRNAs, and transposable elements (TEs), affecting both the varied chromosome (cis-located) and unvaried genome regions (trans-located) across various taxa. While long non-coding RNAs (lncRNAs) are important gene expression regulators, their roles in the context of genomic imbalance remain largely unexplored. In this study, we analyzed and compared the impact of aneuploidy and haploidy/polyploidy on lncRNA expression using RNA-seq data from maize mature leaf tissue. Our results indicate that cis-located lncRNAs are modulated from dosage compensation to a gene dosage effect, while trans-located lncRNAs exhibit trends ranging from an inverse effect to a positive correlation with chromosomal dosage. Remarkably, the ploidy series showed a lesser degree of lncRNA modulation. LncRNAs and TEs display a similar trend of inverse modulation but exhibit greater sensitivity to dosage changes compared to PCGs. The construction of cis-acting and trans-acting lncRNA co-expression networks indicates that lncRNAs likely function as dosage-sensitive regulators of gene expression under conditions of genomic imbalance. Overall, this study not only elucidates the dosage effect of plant lncRNAs but also serves as a valuable resource for exploring potential regulators of PCGs that play significant biological functions.

Zea mays↗

PubMed2000

Demonstration of functional requirement of polypyrimidine tract-binding protein by SELEX RNA during hepatitis C virus internal ribosome entry site-mediated translation initiation.

Polypyrimidine tract-binding protein (PTB) has been previously shown to physically interact with the hepatitis C virus (HCV) RNA genome at its 5'- and 3'-noncoding regions. Using high affinity SELEX RNA molecules, we present evidence for the functional requirement of PTB during HCV internal ribosome entry site (IRES)-controlled translation initiation. This study was carried out in rabbit reticulocyte translation lysates in which the HCV IRES-driven reporter RNA was introduced along with the PTB-specific SELEX RNA molecules. The SELEX RNAs specifically inhibited the HCV IRES function in the context of mono- and dicistronic mRNAs. The cap-dependent translation of a reporter (chloramphenicol acetyltransferase) RNA or naturally capped brome mosaic virus RNA, however, was not affected by the presence of SELEX during in vitro translation assays. The SELEX-mediated inhibition of the HCV IRES is shown to be relieved by the addition of recombinant human PTB in an add-back experiment. The in vivo requirement of PTB was further confirmed by cotransfection of Huh7 cells with reporter RNA and PTB-specific SELEX RNA. The HCV IRES activity was inhibited by the SELEX RNA in these cells, but not by an unrelated control RNA. Together, these results demonstrate the functional requirement of cellular PTB in HCV translation and further support the feasible use of SELEX RNA strategy in demonstrating the functional relevance of cellular protein(s) in complex biological processes.

Base Sequence↗

PubMed2006

Translation repression in human cells by microRNA-induced gene silencing requires RCK/p54.

RNA interference is triggered by double-stranded RNA that is processed into small interfering RNAs (siRNAs) by Dicer enzyme. Endogenously, RNA interference triggers are created from small noncoding RNAs called microRNAs (miRNAs). RNA-induced silencing complexes (RISC) in human cells can be programmed by exogenously introduced siRNA or endogenously expressed miRNA. siRNA-programmed RISC (siRISC) silences expression by cleaving a perfectly complementary target mRNA, whereas miRNA-induced silencing complexes (miRISC) inhibits translation by binding imperfectly matched sequences in the 3' UTR of target mRNA. Both RISCs contain Argonaute2 (Ago2), which catalyzes target mRNA cleavage by siRISC and localizes to cytoplasmic mRNA processing bodies (P-bodies). Here, we show that RCK/p54, a DEAD box helicase, interacts with argonaute proteins, Ago1 and Ago2, in affinity-purified active siRISC or miRISC from human cells; directly interacts with Ago1 and Ago2 in vivo, facilitates formation of P-bodies, and is a general repressor of translation. Disrupting P-bodies by depleting Lsm1 did not affect RCK/p54 interactions with argonaute proteins and its function in miRNA-mediated translation repression. Depletion of RCK/p54 disrupted P-bodies and dispersed Ago2 throughout the cytoplasm but did not significantly affect siRNA-mediated RNA functions of RISC. Depleting RCK/p54 released general, miRNA-induced, and let-7-mediated translational repression. Therefore, we propose that translation repression is mediated by miRISC via RCK/p54 and its specificity is dictated by the miRNA sequence binding multiple copies of miRISC to complementary 3' UTR sites in the target mRNA. These studies also suggest that translation suppression by miRISC does not require P-body structures, and location of miRISC to P-bodies is the consequence of translation repression.

3' Untranslated Regions↗

PubMed1997

Infection with hepatitis G virus and its strain variant, the GB agent (GBV-C), among blood donors in Japan.

BACKGROUND: The purpose of the study was to survey the epidemiology of recently reported non-A through -E hepatitis virus designated hepatitis G virus (HGV) and its strain variant, the GB agent (GBV-C). STUDY DESIGN AND METHODS: Pilot samples from 2461 blood donors in Japan, randomly selected to form cohorts with different levels of alanine aminotransferase (ALT) and markers of hepatitis B virus or hepatitis C virus (HCV) infection, were tested for RNA of HGV/GBV-C by reverse transcription-polymerase chain reaction with nested primers deduced from the 5'-noncoding region. RESULTS: HGV/GBV-C RNA was detected in 23 (7.4%) of the 361 donors with anti-HCV and HCV RNA. This detection is more frequent than that in donors without elevated ALT levels (< or = 45 U/L) or markers of HCV or hepatitis B virus infection (15/1303; 1.2%) (p < 0.001), donors with ALT values between 46 and 99 U per L (0/108) (p < 0.002), donors with ALT values > or = 100 U per L (5/361; 1.4%), and donors with anti-HCV but without detectable HCV RNA (1/93; 1.1%) (p < 0.05). CONCLUSION: More than 1 percent of Japanese blood donors were infected with HGV/GBV-C, and the prevalence was much higher in those with HCV RNA. Should persistent infection with HGV/GBV-C induce any hepatotoxic sequelae, either alone or in concert with the other hepatitis viruses, screening of blood units for HGV/GBV-C would deserve consideration.

Adult↗

PubMed2026

HyLnc: a hybrid deep learning and feature-based approach for long non-coding RNA prediction.

Long non-coding RNAs (lncRNAs) play important roles in gene regulation, development and disease, yet accurate identification of lncRNAs from transcriptomic data remains a major computational challenge. Existing methods often rely either on handcrafted sequence features or deep learning approaches, each with their inherent limitations in capturing the full complexity of RNA sequences. In this study, we proposed HyLnc, a computational framework that integrates transformer-based contextual embeddings with biologically meaningful sequence features for improved lncRNA prediction. A custom BERT-based model was first pre-trained on a large corpus of metazoan RNA sequences using a masked language modelling strategy to learn contextual nucleotide dependencies. The model was subsequently fine-tuned on curated datasets of lncRNAs and protein-coding transcripts and 256-dimensional deep sequence embeddings were extracted. Parallelly, 348 handcrafted features, including ORF characteristics, untranslated region (UTR) properties, nucleotide composition and Fickett scores, were computed. A multi-stage feature selection strategy was applied to identify the most informative features, resulting in optimized hybrid feature sets. Multiple machine learning classifiers were evaluated, with the RF model achieving the best performance. The proposed framework attained an accuracy of 91.30%, F1-score of 91.23% and MCC of 82.60 on an independent validation dataset, outperforming several existing lncRNA prediction tools. Thus, HyLnc demonstrates that integrating deep contextual representations with biologically interpretable features enhances lncRNA prediction. This approach provides a robust and scalable solution for large-scale transcriptome annotation and can be extended to other sequence-based prediction.

RNA, Long Noncoding↗

PubMed2025

Constructing epigenetic regulatory landscapes of plant lncRNAs-an exploration utilizing the novel specialized platform PERlncDB.

Long non-coding RNAs (lncRNAs), once overlooked as transcriptional byproducts, are now recognized for their crucial roles in plant growth, development, and stress responses, with increasing focus on their epigenetic regulation. However, studies investigating epigenomic signals to explore the functions of lncRNAs in plants remain relatively limited. This study collected a comprehensive dataset of over 160 000 high-quality lncRNAs from 19 representative plant species and integrated 6715 ChIP-seq, BS-seq, and RNA-seq datasets to analyze epigenomic patterns at lncRNA loci. Results showed elevated DNA methylation in lncRNA regions. The highest levels occurred in transposable element-associated lncRNAs. Additionally, activating histone modifications at lncRNA loci showed tissue specificity, with epigenetic preferences differed from those at protein-coding gene (PCG) loci. Differential site analysis in epigenetic mutants further highlighted the selective regulation of lncRNA loci by specific epigenetic factors. To facilitate research, we developed PERlncDB, a platform that provides species-specific lncRNA browsing, epigenetic annotation, cross-species conservation analysis, and visualization of epigenomic landscapes. Case studies on MARS and LINC-AP2 emphasized the platform's utility. Conserved epigenetic mechanisms regulating lncRNAs across species, exemplified by a syntenic conserved MET1-regulated lncRNA pair in Arabidopsis and tomato, suggested the stability of regulatory mechanisms underlying lncRNA functions. This work provides critical insights and resources for understanding plant lncRNA epigenetic regulation.

RNA, Long Noncoding↗