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At least 199 records · Page 11Linked to original sources
PubMed2004

The action of ARGONAUTE1 in the miRNA pathway and its regulation by the miRNA pathway are crucial for plant development.

MicroRNAs (miRNAs) are endogenous 21-24-nt RNAs that can down-regulate gene expression by pairing to the messages of protein-coding genes to specify mRNA cleavage or repression of productive translation. They act within the RNA-induced silencing complex (RISC), which in animals contains a member of the Argonaute family of proteins. In the present study, we show that Arabidopsis ago1 mutants have increased accumulation of mRNAs known to be targeted for cleavage by miRNAs. In hypomorphic ago1 alleles, this compromised miRNA function occurs without a substantial change in miRNA accumulation, whereas in null alleles it is accompanied by a drop in some of the miRNAs. Therefore, AGO1 acts within the Arabidopsis miRNA pathway, probably within the miRNA-programmed RISC, such that the absence of AGO1 destabilizes some of the miRNAs. We also show that targeting of AGO1 mRNA by miR168 is needed for proper plant development, illustrating the importance of feedback control by this miRNA. Transgenic plants expressing a mutant AGO1 mRNA with decreased complementarity to miR168 overaccumulate AGO1 mRNA and exhibit developmental defects partially overlapping with those of dcl1, hen1, and hyl1 mutants showing a decrease in miRNA accumulation. miRNA targets overaccumulate in miR168-resistant plants, suggesting that a large excess of AGO1 protein interferes with the function of RISC or sequesters miRNAs or other RISC components. Developmental defects induced by a miR168-resistant AGO1 mRNA can be rescued by a compensatory miRNA that is complementary to the mutant AGO1 mRNA, proving the regulatory relationship between miR168 and its target and opening the way for engineering artificial miRNAs in plants.

Amino Acid Sequence↗
PubMed2025

The MIR169:NF-YA module enhances biomass and yield via ARGOS in Arabidopsis and tomato.

Molecular links between miRNA: target modules regulating downstream genes for crop maturation/yield are poorly understood. Here, we report that elevated miR169d expression and concomitant reduced NF-YA2 (Nuclear Factor-Y subunit-A) target levels positively regulate vegetative growth and yield in Arabidopsis along with a shorter life cycle. In agreement, increased NF-YA2 levels in (1) NF-YA2-OE (overexpression) lines, (2) miR169d-target-mimicry lines (in which miR169d is chelated), and (3) miR169d-non-cleavable NF-YA2 resistant target lines show the opposite phenotype. Further, we find increased auxin levels in MIR169d-OE and nf-ya2 mutant lines, supporting the enrichment of 'auxin terms' in MIR169-OE transcriptome data. We show that ARGOS (auxin-regulated gene involved in organ size) is upregulated in MIR169d-OE due to reduced NF-YA2 repressor levels and that NF-YA2 directly binds the ARGOS promoter. Genetic screens of this module show that neither overexpressing miR169d in an argos mutant background nor the nf-ya2:argos double mutants rescue the argos mutant phenotype, suggesting a parallel pathway of ARGOS regulation via the MIR169:NF-YA2 node, independent of auxin. To assess the translational potential of this module in a crop, we show that Sly-MIR169-OE lines in tomato, having reduced target Sly-NF-YA10 levels, also regulate Sly-ARGOS resulting in early flowering, larger sized fruits, more fruit fresh weight, higher fruit set, early fruiting, and better shelf life than wild-type plants. In contrast, Sly-STTM169 plants inhibited for Sly-miR169 action and having increased levels of Sly-NF-YA10 have a longer life cycle with reduced biomass, decreased fruit set, and an overall reduction in yield. Thus, our findings show a conserved MIR169:NF-YA:ARGOS module which can be applied to crops for addressing future food demands.

MicroRNAs↗
PubMed2002

MicroRNAs in plants.

MicroRNAs (miRNAs) are an extensive class of ~22-nucleotide noncoding RNAs thought to regulate gene expression in metazoans. We find that miRNAs are also present in plants, indicating that this class of noncoding RNA arose early in eukaryotic evolution. In this paper 16 Arabidopsis miRNAs are described, many of which have differential expression patterns in development. Eight are absolutely conserved in the rice genome. The plant miRNA loci potentially encode stem-loop precursors similar to those processed by Dicer (a ribonuclease III) in animals. Mutation of an Arabidopsis Dicer homolog, CARPEL FACTORY, prevents the accumulation of miRNAs, showing that similar mechanisms direct miRNA processing in plants and animals. The previously described roles of CARPEL FACTORY in the development of Arabidopsis embryos, leaves, and floral meristems suggest that the miRNAs could play regulatory roles in the development of plants as well as animals.

Base Sequence↗
PubMed2026

Decoding the molecular basis of blue grain color codominance in Qingke: Integrative analysis of RNA-seq, DNA methylation, and miRNA-seq.

The grains on single spike of the F1 generation from the cross between blue- and white-grained Qingke (Hordeum vulgare L. var. nudum Hook. f.) are randomly distributed in blue and white colors. This study integrated data from RNA-seq, DNA methylation, and miRNA-seq to analyze this trait. The results showed that the HvF3'5'H gene is likely central to the development of this codominant phenotype. Through cross-validation of three omics approaches, it was found that the HvMYB gene targeted by miR858-z, as well as the WRKY24 and At3g44326 genes targeted by novel-m0152-5p, novel-m0153-5p, and novel-m0154-5p, are correlated with DNA methylation. qRT-PCR analysis confirmed that the four aforementioned genes exhibited variety-specific and developmental stage-specific expression patterns. This study dissects the regulatory network underlying the codominant blue and white grain color divergence on a single Qingke spike from a multi-omics perspective.

DNA Methylation↗
PubMed2003

Regulation by RNA.

In recent years, noncoding RNAs (ncRNAs) have been shown to constitute key elements implicated in a number of regulatory mechanisms in the cell. They are present in bacteria and eukaryotes. The ncRNAs are involved in regulation of expression at both transcriptional and posttranscriptional levels, by mediating chromatin modifications, modulating transcription factor activity, and influencing mRNA stability, processing, and translation. Noncoding RNAs play a key role in genetic imprinting, dosage compensation of X-chromosome-linked genes, and many processes of differentiation and development.

Animals↗
PubMed2004

STAT1 binds to the herpes simplex virus type 1 latency-associated transcript promoter.

The authors hypothesized that environmental stimuli induce cytokines that act through an intracellular cascade, which includes signal transducers and activators of transcription (STATs), to change herpes simplex virus (HSV) gene expression, thereby inducing viral reactivation. The HSV type 1 (HSV-1) latency-associated transcript (LAT) gene regulates viral reactivation within neurons via an unknown mechanism. HSV-1 deletion mutants that are missing key portions of the LAT gene, particularly the 3' region of the LAT promoter, do not reactivate normally in vivo. The authors hypothesized that STAT transcription factors may bind in this region to regulate viral reactivation. Electrophoretic mobility shift assay (EMSA) experiments were performed by incubating mouse trigeminal ganglion (TG) nuclear extracts with each of three overlapping sequences representing the 3' region of the HSV-1 LAT promoter (referred to as oligos L1, L2, and L3). The ganglionic nuclear extracts bound specifically to oligos L1 and L3, but not L2. Oligos L1 and L3 contain predicted STAT binding sequences whereas L2 does not. Specific binding to oligo L3 (including the TATA box sequence) was supershifted by incubating with anti-STAT1 antibodies, but not by incubating with anti-STAT3 or anti-STAT5a antibodies. Specific L3 binding was reduced by competing with excess unlabeled STAT1 consensus sequences. These results indicate that STAT1, probably as part of a complex, is capable of binding to the LAT promoter on or near the TATA box. Further studies are required to determine if STAT1 is required for LAT expression in vivo. This work supports the hypothesis that interferons act through STAT1 to regulate the expression of HSV-1 LAT.

Animals↗
PubMed2004

The long hand of the small RNAs reaches into several levels of gene regulation.

Small RNA molecules such as siRNAs and miRNAs represent a new class of molecules that have been implicated in a wide range of diverse gene silencing phenomena. It is now becoming clear that these two similar molecules share several common features in both their biogenesis and their mechanism of action. Thus, the siRNA and miRNA pathways may have evolved from a common ancestral mechanism that has diverged to play important roles in developmental regulation, genomic organisation, and cellular defence against foreign nucleic acids.

Animals↗
PubMed2026

First insights into the miRNA landscape of Tursiops truncatus milk reveal shared dominant microRNA families with terrestrial mammals.

MicroRNAs (miRNAs) are small non-coding RNAs that play crucial regulatory roles in gene expression in metazoans. While the miRNA repertoire and relative abundances have been extensively studied in terrestrial mammals, no information was available for the milk of marine mammals. Here, we present the first characterization of the miRNA genomic landscape and abundance in milk in the bottlenose dolphin (Tursiops truncatus). Using a sequence-based comparative approach, we identified 186 conserved miRNA families comprising 354 high-confidence precursors in the dolphin genome. Comparative analysis across 52 cetacean genomes revealed a small number of lineage-specific loss events, such as mir-187 in Delphinidae, and the absence of nine miRNA families in all cetaceans. Small RNA sequencing from pooled milk samples confirmed the detectable abundance of 119 miRNAs, with a landscape dominated by mir-148, let-7, mir-8, and mir-21, collectively accounting for over 70% of total miRNA reads. These dominant families include miRNAs frequently reported in the milk of terrestrial mammals, suggesting qualitative similarity in the major milk miRNA repertoire between dolphin and terrestrial mammals. These findings should be interpreted as a first sequencing-supported exploratory characterization of dolphin milk miRNAs.

Animals↗
PubMed2003

Dissection of floral induction pathways using global expression analysis.

Flowering of the reference plant Arabidopsis thaliana is controlled by several signaling pathways, which converge on a small set of genes that function as pathway integrators. We have analyzed the genomic response to one type of floral inductive signal, photoperiod, to dissect the function of several genes transducing this stimulus, including CONSTANS, thought to be the major output of the photoperiod pathway. Comparing the effects of CONSTANS with those of FLOWERING LOCUS T, which integrates inputs from CONSTANS and other floral inductive pathways, we find that expression profiles of shoot apices from plants with mutations in either gene are very similar. In contrast, a mutation in LEAFY, which also acts downstream of CONSTANS, has much more limited effects. Another pathway integrator, SUPPRESSOR OF OVEREXPRESSION OF CO 1, is responsive to acute induction by photoperiod even in the presence of the floral repressor encoded by FLOWERING LOCUS C. We have discovered a large group of potential floral repressors that are down-regulated upon photoperiodic induction. These include two AP2 domain-encoding genes that can repress flowering. The two paralogous genes, SCHLAFMUTZE and SCHNARCHZAPFEN, share a signature with partial complementarity to the miR172 microRNA, whose precursor we show to be induced upon flowering. These and related findings on SPL genes suggest that microRNAs play an important role in the regulation of flowering.

Animals↗
PubMed2026

A Comparative Analysis of the Methylation Status of Non-Coding RNA Promoters in Fibroid and Matched Myometrium.

Uterine fibroids exhibit dysregulated expression of non-coding RNAs (ncRNAs), although the underlying mechanisms remain incompletely understood. We investigated promoter DNA methylation and its relationship with ncRNA expression in fibroids. Genomic DNA from eight paired fibroid and matched myometrial tissues was analyzed using MeDIP-chip to identify differentially methylated ncRNA promoters. Selected candidates were validated by methylation-specific PCR (MSP) in 16 paired samples, and transcript expression was assessed by qRT-PCR in 68-94 paired specimens. MeDIP-chip identified 538 lncRNAs and 61 miRNAs with differential promoter methylation, including 300 hypermethylated and 238 hypomethylated lncRNAs and 47 hypermethylated and 14 hypomethylated miRNAs. Promoter methylation was not significantly correlated with transcript expression (r = -0.1224). MSP confirmed hypermethylation of LINC-PINT and MIR9-3 and hypomethylation of WT1-AS and TTLL10-AS1. Correspondingly, LINC-PINT and MIR9-3 expression was decreased, whereas WT1-AS and TTLL10-AS1 expression was increased in fibroids. However, LINC-PINT and TTLL10-AS1 methylation did not fully correspond with MeDIP-chip findings. These results reveal widespread ncRNA promoter methylation alterations in uterine fibroids but demonstrate that genome-wide methylation does not consistently predict transcript expression, highlighting the complexity of ncRNA epigenetic regulation and the importance of locus-specific validation.

Humans↗
PubMed2025

MicroRNA-486: a dual-function biomarker for diagnosis and tumor immune microenvironment characterization in non-small cell lung cancer.

BACKGROUND: This investigation evaluates the clinical significance and molecular mechanisms of microRNA-486 (miR-486) as a potential biomarker in non-small cell lung cancer (NSCLC) through an integrative analytical approach. METHODS: We conducted systematic search and meta-analysis of diagnostic studies from major biomedical databases from inception through April 04, 2025, followed by comprehensive bioinformatics interrogation. Protein-protein interaction (PPI) networks were constructed using STRING to identify key hub genes regulated by miR-486. Validation of hub genes employed TCGA datasets, while immune infiltration analysis utilized TIMER2.0 platform. RESULTS: The meta-analysis indicated that miR-486, both individually and in combination, could be effective biomarkers for NSCLC detection. Afterwards, functional enrichment analyses of miR-486 target genes highlighted significant ontology terms and pathways crucial to the initiation and progression of NSCLC. PPI networks revealed key proteins and modules that participate in multiple essential pathways associated with NSCLC pathogenesis. Furthermore, the identified hub genes were validated for differential expression in cancerous versus normal tissues, suggesting their potential diagnostic utility, while subsequent survival analyses confirmed their prognostic value through significant associations with overall survival. Notably, these hub genes were found to be significantly associated with immune infiltration levels, immune microenvironment scores, and immune-related proteins in NSCLC. CONCLUSIONS: This dual-modality investigation establishes miR-486 as a multi-functional biomarker in NSCLC, demonstrating both diagnostic utility and immunoregulatory potential through tumor microenvironment modulation.

Humans↗
PubMed2003

Identification of many microRNAs that copurify with polyribosomes in mammalian neurons.

Localized translation in mammalian dendrites may play a role in synaptic plasticity and contribute to the molecular basis for learning and memory. The regulatory mechanisms that control localized translation in neurons are not well understood. We propose a role for microRNAs (miRNAs), a class of noncoding RNAs, as mediators of neuronal translational regulation. We have identified 86 miRNAs expressed in mammalian neurons, of which 40 have not previously been reported. A subset of these miRNAs exhibits temporally regulated expression in cortical cultures. Moreover, all of the miRNAs that were tested cofractionate with polyribosomes, the sites of active translation. These findings indicate that a large, diverse population of miRNAs may function to regulate translation in mammalian neurons.

Animals↗
PubMed2025

Interconnected study of molecular pathways: miR-137 as a central element at the intersection of lipid metabolism and prostate carcinogenesis.

OBJECTIVE: To evaluate the roles of miR-137 and its target genes in lipid metabolism and prostate tumorigenesis. METHODS: We used a series of bioinformatic approaches to establish the relationship between miR-137 and its target genes. We mapped the metabolic pathways of interest in the Reactome database and identified the central target genes of miR-137 in this pathway using four platforms: Reactome, miRDB, miRmap, and TargetScan. To assess the expression and association with clinical parameters, we obtained information from the UALCAN, OncoDB, and GEPIA2 databases using a dataset of patients with prostate cancer from The Cancer Genome Atlas. For functional enrichment analysis and construction of the protein-protein interaction network, we used the Kyoto Encyclopedia of Genes and Genomes, Gene Ontology, and STRING. RESULTS: Our in silico study of The Cancer Genome Atlas database revealed that miR-137 is underexpressed in tumor tissues, and its reduction is associated with poor prognosis. An intriguing set of eight genes within the PPARα pathway: PPARGC1A, PPARGC1B, NCOA1, NCOA2, NCOA3, MED1, MED27, and ESRRA displayed synergy, positive correlations, and synchronized expression patterns in adipose, hepatic, and prostatic tissues, all linked to the enigmatic processes of metabolic regulation. Among the highlighted genes, ESRRA was overexpressed in the malignant environment, whereas its counterparts remained underexpressed. The plot was thickened with associations between the expression of NCOA1, NCOA3, and MED27, lymph node involvement, and the overexpression of several genes linked to advanced prostate cancer stages. An intriguing pattern emerged, with patients exhibiting reduced disease-free survival overexpressing NCOA2, NCOA3, MED27, and ESRRA. CONCLUSION: This study elucidates the possibility that miR-137 subtly modulates metabolic genes in prostate cancer, suggesting its latent therapeutic potential as a biomarker for disease progression. BACKGROUND: ■ The reduction of miR-137 in tumor tissues is associated with a worse prognosis. BACKGROUND: ■ miR-137 has eight oncogenically relevant target genes acting in the PPARα lipid pathway. BACKGROUND: ■ NCOA1, NCOA3, MED27, and ESRRA are associated with advanced prostate cancer. BACKGROUND: ■ miR-137 exhibits significant clinical potential by repressing the activation of pathways that influence prostate tumorigenesis in hyperstimulated metabolic environments. BACKGROUND: Prostate cancer progression is sustained by the simultaneous activation of pathways involving lipid uptake and de novo synthesis. In this context, miR-137 inhibits adipogenic differentiation and may reduce lipid uptake by tumor cells by modulating the PPAR/ p160/ESRRA axis, considerably attenuating metabolic effects and suppressing prostate tumorigenesis.

Male↗
PubMed2004

Probing the microRNA and small interfering RNA pathways with virus-encoded suppressors of RNA silencing.

In plants, small interfering RNAs (siRNAs) and microRNAs (miRNAs) are effectors of RNA silencing, a process involved in defense through RNA interference (RNAi) and in development. Plant viruses are natural targets of RNA silencing, and as a counterdefensive strategy, they have evolved highly diverse silencing suppressor proteins. Although viral suppressors are usually thought to act at distinct steps of the silencing machinery, there had been no consensus system so far that allowed a strict side-by-side analysis of those factors. We have set up such a system in Arabidopsis thaliana and used it to compare the effects of five unrelated viral silencing suppressors on the siRNA and miRNA pathways. Although all the suppressors inhibited RNAi, only three of them induced developmental defects, indicating that the two pathways are only partially overlapping. These developmental defects were remarkably similar, and their penetrance correlated with inhibition of miRNA-guided cleavage of endogenous transcripts and not with altered miRNA accumulation per se. Among the suppressors investigated, the tombusviral P19 protein coimmunoprecipitated with siRNA duplexes and miRNA duplexes corresponding to the primary cleavage products of miRNA precursors. Thus, it is likely that P19 prevents RNA silencing by sequestering both classes of small RNAs. Moreover, the finding here that P19 binds siRNAs and suppresses RNAi in Hela cells also suggests that this factor may be useful to dissect the RNA silencing pathways in animals. Finally, the differential effects of the silencing suppressors tested here upon other types of Arabidopsis silencing-related small RNAs revealed a surprising variety of biosynthetic and, presumably, functional pathways for those molecules. Therefore, silencing suppressors are valuable probes of the complexity of RNA silencing.

Arabidopsis↗
PubMed2026

MicroRNAs and predicted targets in the switch from monolayered to spheroids of cholangiocarcinoma cells.

BACKGROUND: Extrahepatic cholangiocarcinoma (eCCA) is characterized by marked molecular heterogeneity and limited therapeutic options. MicroRNAs (miRNAs) are key post-transcriptional regulators of cancer-related pathways, but their contribution to tumor adaptation in physiologically relevant models remains poorly understood. Three-dimensional (3D) tumor spheroids better mimic in vivo conditions than conventional two-dimensional (2D) cultures. METHODS: We compared miRNA expression profiles in two eCCA cell lines (Sk-ChA-1 and Mz-ChA-1) grown as monolayers (2D) or multicellular tumor spheroids (3D). MiRNA profiling was performed using NanoString technology. Predicted targets were analyzed by over-representation analysis, and selected miRNAs and genes were validated by RT-qPCR and ELISA-based assays. RESULTS: 3D growth induced extensive miRNA remodeling, with distinct (54 deregulated in Sk-ChA-1 and 29 in Mz-ChA-1 cells) and partially overlapping signatures (miR-1283, miR-577, and miR-2113). Among the shared miRNAs, predicted targets included DUSP10 and RBFOX1, while in spheroids, cell-specific multiple miRNAs converged on shared targets (TNRC6B, SMARCAD1, ATG14, HMGA2, and CLOCK) displaying inverse expression patterns. The transcriptional program impacted MAPK signaling, enhanced EMT, and activated stress-adaptive networks but attenuated proliferation in 3D Sk-ChA-1 cells, while Mz-ChA-1 cells retained a more epithelial and proliferative profile. In this context, we point out the involvement of miR-19b-3p using anti-miR transfection experiments. CONCLUSION: Our findings reveal a miRNA-driven regulatory landscape associated with 3D growth in eCCA, linking tumor architecture to signaling rewiring and cellular plasticity, and highlight potentially druggable candidate targets and pathways to investigate as candidates using inhibitors or gene therapy-based interventions.

Humans↗
PubMed2003

A microRNA as a translational repressor of APETALA2 in Arabidopsis flower development.

Plant microRNAs (miRNAs) show a high degree of sequence complementarity to, and are believed to guide the cleavage of, their target messenger RNAs. Here, I show that miRNA172, which can base-pair with the messenger RNA of a floral homeotic gene, APETALA2, regulates APETALA2 expression primarily through translational inhibition. Elevated miRNA172 accumulation results in floral organ identity defects similar to those in loss-of-function apetala2 mutants. Elevated levels of mutant APETALA2 RNA with disrupted miRNA172 base pairing, but not wild-type APETALA2 RNA, result in elevated levels of APETALA2 protein and severe floral patterning defects. Therefore, miRNA172 likely acts in cell-fate specification as a translational repressor of APETALA2 in Arabidopsis flower development.

Antisense Elements (Genetics)↗