Project description:Hypertrophic cardiomyopathy (HCM) represents one of the most common heritable heart diseases. However, the signalling pathways and regulatory networks underlying the pathogenesis of HCM remain largely unknown. Here, we present a strand-specific RNA-seq dataset for both coding and lncRNA profiling in myocardial tissues from 28 HCM patients and 9 healthy donors. This dataset constitutes a valuable resource for the community to examine the dysregulated coding and lncRNA genes in HCM versus normal conditions.
Project description:The expression of the long non-coding RNAs (lncRNAs) in the active tuberculosis patients,multidrug-resistant tuberculosis patients,cured tuberculosis subjects and healthy controls were scanned using lncRNA microarray.The Arraystar Human LncRNA Microarray version 4.0 (Agilent Technologies) was used,containing 40173 lncRNA probes and 20730 mRNA probes for the detection of lncRNAs and mRNAs in the sample. Non-coding RNAs and mRNAs profiling by array
Project description:We report the application of RNA-sequencing technology for high-throughput profiling of Drosophila that express clinical variants of feline-MyBPC3 associated with Hypertrophic Cardiomyopathy (HCM).
2020-12-04 | GSE141574 | GEO
Project description:Long QTc in hypertrophic cardiomyopathy
Project description:The role of long noncoding RNA (lncRNA) in adult hearts is unknown; also unclear is how lncRNA modulates nucleosome remodelling. An estimated 70% of mouse genes undergo antisense transcription1, including myosin heavy chain 7 (Myh7), which encodes molecular motor proteins for heart contraction2. Here we identify a cluster of lncRNA transcripts from Myh7 loci and demonstrate a new lncRNA–chromatin mechanism for heart failure. In mice, these transcripts, which we named myosin heavy-chain-associated RNA transcripts (Mhrt), are cardiac-specific and abundant in adult hearts. Pathological stress activates the Brg1–Hdac–Parp chromatin repressor complex3 to inhibit Mhrt transcription in the heart. Such stress-induced Mhrt repression is essential for cardiomyopathy to develop: restoring Mhrt to the pre-stress level protects the heart from hypertrophy and failure. Mhrt antagonizes the function of Brg1, a chromatin-remodelling factor that is activated by stress to trigger aberrant gene expression and cardiac myopathy3. Mhrt prevents Brg1 from recognizing its genomic DNA targets, thus inhibiting chromatin targeting and gene regulation by Brg1. It does so by binding to the helicase domain of Brg1, a domain that is crucial for tethering Brg1 to chromatinized DNA targets. Brg1 helicase has dual nucleic-acid-binding specificities: it is capable of binding lncRNA (Mhrt) and chromatinized—but not naked—DNA. This dual-binding feature of helicase enables a competitive inhibition mechanism by which Mhrt sequesters Brg1 from its genomic DNA targets to prevent chromatin remodelling. A Mhrt–Brg1 feedback circuit is thus crucial for heart function. Human MHRT also originates from MYH7 loci and is repressed in various types of myopathic hearts, suggesting a conserved lncRNA mechanism in human cardiomyopathy. Our studies identify a cardioprotective lncRNA, define a new targeting mechanism for ATP-dependent chromatin-remodelling factors, and establish a new paradigm for lncRNA–chromatin interaction. Overexpression of murine non-coding RNAs in human cell line, comparison of RNA-sequencing with Ribosome Profiling
Project description:Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA (lncRNA) that was first discovered as a prognostic marker for lung cancer metastasis. MALAT1 has been implicated in the tumorigenesis of numerous tumor types. To further delineate the underlying molecular mechanism, we established a high-throughput strategy to characterize the interacting proteins of MALAT1 by combining RNA pull down, quantitative proteomics, bioinformatics analysis, and experimental validation.
Project description:Dilated cardiomyopathy (DCM) is characterized by left ventricular dilation and continuous systolic dysfunction. Mitochondrial impairment is critical in DCM, but the mechanism remains to be elucidated. Here we explored the cardio-protective role of a heart-enriched long non-coding RNA (lncRNA), named dilated cardiomyopathy repressive transcript (DCRT), via maintaining mitochondrial function. We found the lncRNA DCRT was highly enriched in normal heart tissue and its expression was significantly down-regulated in myocardium of DCM patients. DCRT knockout in mice spontaneously developed cardiac dysfunction with cardiac enlargement and mitochondrial impairment. DCRT transgenic or overexpressed mice attenuated cardiac dysfunction induced by transverse aortic constriction (TAC) treatment.
Project description:Long non-coding RNAs (lncRNAs) are defined as non-protein-coding transcripts that are at least 200 nucleotides long. They are known to play pivotal roles in regulating gene expression, especially during stress responses in plants. We used a large collection of in-house transcriptome data from various soybean (Glycine max and Glycine soja) tissues treated under different conditions to perform a comprehensive identification of soybean lncRNAs. We also retrieved publicly available soybean transcriptome data that were of sufficient quality and sequencing depth to enrich our analysis. In total, RNA-seq data of 332 samples were used for this analysis. An integrated reference-based, de novo transcript assembly was developed that identified ~69,000 lncRNA gene loci. We showed that lncRNAs are distinct from both protein-coding transcripts and genomic background noise in terms of length, number of exons, transposable element composition, and sequence conservation level across legume species. The tissue-specific and time-specific transcriptional responses of the lncRNA genes under some stress conditions may suggest their biological relevance. The transcription start sites of lncRNA gene loci tend to be close to their nearest protein-coding genes, and they may be transcriptionally related to the protein-coding genes, particularly for antisense and intronic lncRNAs. A previously unreported subset of small peptide-coding transcripts was identified from these lncRNA loci via tandem mass spectrometry, which paved the way for investigating their functional roles. Our results also highlight the current inadequacy of the bioinformatic definition of lncRNA, which excludes those lncRNA gene loci with small open reading frames (ORFs) from being regarded as protein-coding.