Similar Datasets
Project description:To investigate roles for olfactory receptor coding sequence mRNA in trans olfactory receptor gene silencing, and OR-gene enhancer recruitment. Olfactory receptor (OR) choice provides an extreme example of allelic competition for transcriptional dominance, as every olfactory neuron stably transcribes one out of more than ~2,000 OR alleles1,2. OR gene choice is mediated by a multi-chromosomal enhancer hub that activates transcription at a single OR3,4, followed by ORtranslation dependent feedback that stabilizes this choice5,6. However, with more than one OR enhancer hub in each nucleus7, the mechanism by which only one OR allele is chosen for transcription remains enigmatic. Here, using single cell genomics, we show that only one of the OR enhancer hubs formed in each neuron retains euchromatic features and sustains transcriptional competence. Further, we provide evidence that OR transcription recruits enhancers and reinforces enhancer hub activity locally, while OR RNA inhibits transcription in competing hubs over distance, promoting OR protein-independent transition to singularity. While OR RNA synthesis is sufficient to break the symmetry between equipotent enhancer hubs, OR translation stabilizes transcription at the prevailing hub, revealing dual non-coding and coding mechanisms implemented by OR RNAs for transcriptional prevalence. We propose that coding mRNAs can function as “selfish” non-coding RNAs that influence nuclear architecture, enhance their own transcription, and inhibit their competitors, with generalizable implications in probabilistic cell fate decisions.
2023-09-28 | GSE240023 | GEO
Project description:To investigate roles for olfactory receptor coding sequence mRNA in trans olfactory receptor gene silencing, and OR-gene enhancer recruitment. Olfactory receptor (OR) choice provides an extreme example of allelic competition for transcriptional dominance, as every olfactory neuron stably transcribes one out of more than ~2,000 OR alleles1,2. OR gene choice is mediated by a multi-chromosomal enhancer hub that activates transcription at a single OR3,4, followed by ORtranslation dependent feedback that stabilizes this choice5,6. However, with more than one OR enhancer hub in each nucleus7, the mechanism by which only one OR allele is chosen for transcription remains enigmatic. Here, using single cell genomics, we show that only one of the OR enhancer hubs formed in each neuron retains euchromatic features and sustains transcriptional competence. Further, we provide evidence that OR transcription recruits enhancers and reinforces enhancer hub activity locally, while OR RNA inhibits transcription in competing hubs over distance, promoting OR protein-independent transition to singularity. While OR RNA synthesis is sufficient to break the symmetry between equipotent enhancer hubs, OR translation stabilizes transcription at the prevailing hub, revealing dual non-coding and coding mechanisms implemented by OR RNAs for transcriptional prevalence. We propose that coding mRNAs can function as “selfish” non-coding RNAs that influence nuclear architecture, enhance their own transcription, and inhibit their competitors, with generalizable implications in probabilistic cell fate decisions.
2023-09-28 | GSE232194 | GEO
Project description:Olfactory receptor mRNAs act as selfish non-coding RNAs that enforce transcriptional singularity
| PRJNA960870 | ENA
Project description:Olfactory receptor mRNAs act as selfish non-coding RNAs that enforce transcriptional singularity (OR Switching Experiment)
| PRJNA1001933 | ENA
Project description:Olfactory receptor mRNAs act as selfish non-coding RNAs that enforce transcriptional singularity (Non-coding OR Hi-C & RNA-seq)
| PRJNA971200 | ENA
Project description:Age-related decline in olfactory function affects the quality of life in elderly people and also potentially represents an early clinical symptom of neurodegenerative disorder. Olfactory bulb (OB) plays a central role in olfactory information transmitting and signal processing. The mechanisms underlying this impairment remain unclear. In the current study, microarray was used to investigate differentially expressed protein coding genes (PCGs) and long non-coding RNAs (lncRNAs) in OBs from three groups of mice of different ages (2 months-old young adults, 6 months-old mature adults and 20 months-old aged adults), for their potential roles in olfactory impairment. Gene Ontology and pathway analysis results showed that the differentially expressed PCGs in the OBs from aged mice were mainly associated with signal transduction, regulation of gene expression and cellular microenvironment. Similarly, gene set enrichment analysis identified two differentially and inversely expressed lncRNAs (NONMMUT004524 and NONMMUT000384), both of which were significantly associated with neuroactive ligand-receptor interaction pathway in the OBs of aged mice. These findings suggest that a decline of olfactory function in aged mice may be linked to differential expression of specific lncRNAs and their potentially adverse effects on the neuroactive ligand-receptor interaction pathway in the OB.
| S-EPMC5437011 | biostudies-literature
Project description:Olfactory receptor (Olfr) genes comprise the largest gene family in mice. Despite their importance in olfaction, how most Olfr mRNAs are regulated remains unexplored. Using RNA-seq analysis coupled with analysis of pre-existing databases, we found that Olfr mRNAs have several atypical features suggesting that post-transcriptional regulation impacts their expression. First, Olfr mRNAs, as a group, have dramatically higher average AU-content and lower predicted secondary structure than do control mRNAs. Second, Olfr mRNAs have a higher density of AU-rich elements (AREs) in their 3'UTR and upstream open reading frames (uORFs) in their 5 UTR than do control mRNAs. Third, Olfr mRNAs have shorter 3' UTR regions and with fewer predicted miRNA-binding sites. All of these novel properties correlated with higher Olfr expression. We also identified striking differences in the post-transcriptional features of the mRNAs from the two major classes of Olfr genes, a finding consistent with their independent evolutionary origin. Together, our results suggest that the Olfr gene family has encountered unusual selective forces in neural cells that have driven them to acquire unique post-transcriptional regulatory features. In support of this possibility, we found that while Olfr mRNAs are degraded by a deadenylation-dependent mechanism, they are largely protected from this decay in neural lineage cells.
| S-EPMC4627058 | biostudies-literature
Project description:Genome-wide transcriptomic studies in humans and mice have become extensive and mature. However, a comprehensive and systematic understanding of protein-coding genes and long non-coding RNAs (lncRNAs) expressed during pig spleen development has not been achieved. LncRNAs are known to participate in regulatory networks for an array of biological processes. Here, we constructed 18 RNA libraries from developing fetal pig spleen (55 days before birth), postnatal pig spleens (0, 30, 180 days and 2 years after birth), and the samples from the 2-year-old Wild Boar. A total of 15,040 lncRNA transcripts were identified among these samples. We found that the temporal expression pattern of lncRNAs was more restricted than observed for protein-coding genes. Time-series analysis showed two large modules for protein-coding genes and lncRNAs. The up-regulated module was enriched for genes related to immune and inflammatory function, while the down-regulated module was enriched for cell proliferation processes such as cell division and DNA replication. Co-expression networks indicated the functional relatedness between protein-coding genes and lncRNAs, which were enriched for similar functions over the series of time points examined. We identified numerous differentially expressed protein-coding genes and lncRNAs in all five developmental stages. Notably, ceruloplasmin precursor (CP), a protein-coding gene participating in antioxidant and iron transport processes, was differentially expressed in all stages. This study provides the first catalog of the developing pig spleen, and contributes to a fuller understanding of the molecular mechanisms underpinning mammalian spleen development.
| S-EPMC5851557 | biostudies-literature
Project description:The dysregulation of long non-coding RNAs (lncRNAs) is associated with the development of various diseases. However, little is known about the regulatory function of lncRNAs in peritendinous fibrosis. Therefore, the expression profiles of lncRNAs and mRNAs in normal tendon and fibrotic peritendinous tissues were analyzed in this study using RNA sequencing. In total, 219 lncRNAs and 3403 mRNAs were identified that were differentially expressed between the two sets of tissues. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that the dysregulated mRNAs were mainly associated with immune regulation, inflammation, extracellular matrix (ECM) production and remodeling, and cell cycle regulation. An lncRNA-mRNA co-expression network revealed 181 network pairs comprising eight dysregulated lncRNAs and 146 mRNAs. The results of the bioinformatics analysis indicated that the dysregulated lncRNAs play a role in fibrogenesis through regulation of the cell cycle, inflammation, and ECM production. Furthermore, silencing the lncRNA dnm3os prevented transforming growth factor (TGF)-?1-induced tenocyte proliferation and expression of genes related to fibrogenesis. These findings provide a basis for investigations into the regulatory mechanisms underlying the development and progression of peritendinous fibrosis.
| S-EPMC6300459 | biostudies-literature
Project description:In recent years, diagnostic and therapeutic approaches for rheumatoid arthritis (RA) have continued to improve. However, in the advanced stages of the disease, patients are unable to achieve long-term clinical remission and often suffer from systemic multi-organ damage and severe complications. Patients with RA usually have no overt clinical manifestations in the early stages, and by the time a definitive diagnosis is made, the disease is already at an advanced stage. RA is diagnosed clinically and with laboratory tests, including the blood markers C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) and the autoantibodies rheumatoid factor (RF) and anticitrullinated protein antibodies (ACPA). However, the presence of RF and ACPA autoantibodies is associated with aggravated disease, joint damage, and increased mortality, and these autoantibodies have low specificity and sensitivity. The etiology of RA is unknown, with the pathogenesis involving multiple factors and clinical heterogeneity. The early diagnosis, subtype classification, and prognosis of RA remain challenging, and studies to develop minimally invasive or non-invasive biomarkers in the form of biofluid biopsies are becoming more common. Non-coding RNA (ncRNA) molecules are composed of long non-coding RNAs, small nucleolar RNAs, microRNAs, and circular RNAs, which play an essential role in disease onset and progression and can be used in the early diagnosis and prognosis of RA. In this review of the diagnostic and prognostic approaches to RA disease, we provide an overview of the current knowledge on the subject, focusing on recent advances in mRNA-ncRNA as diagnostic and prognostic biomarkers from the biofluid to the tissue level.
| S-EPMC9929281 | biostudies-literature