Paraspeckle protein NONO attenuates vascular calcification by inhibiting BMP2 transcription
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ABSTRACT:
PROVIDER: PRJNA1058999 | ENA |
REPOSITORIES: ENA
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Project description:Vascular calcification is a common and life-threatening complication in patients with chronic kidney disease, in which osteogenic differentiation of vascular smooth muscle cells (VSMCs) plays an essential role. Paraspeckle protein NONO is a multifunctional protein involved in many nuclear biological processes but its role in vascular calcification and osteogenic differentiation of VSMCs remains unclear.By RNA sequencing analysis in primary mouse VSMCs with or without NONO knockout, we observed significant changes of genes important in regulating vascular function and osteogenic differentiation of VSMCs.
2024-01-10 | GSE252244 | GEO
Project description:Renal disease is a major risk factor for cardiovascular disease. BMP2 and its downstream effectors are strong implicators of pathological calcificatoin. We profiled miRNAs from Klotho mutant mice and from health mice to determine any potential biomarkers for predicting the progression of pathological calcification through targeting of BMP2 and its downstream effectors.
2020-10-27 | GSE135759 | GEO
Project description:MiRNA-mediated regulation of Bmp2 during pathological calcification
| PRJNA559924 | ENA
Project description:Non-POU domain-containing octamer-binding protein (NONO) is a multifunctional member of the Drosophila behavior/human splicing (DBHS) protein family with DNA- and RNA-binding activity. Recent studies revealed that NONO is O-GlcNAcylated and dysregulated in various types of cancer. Excessive O-GlcNAcylation of target proteins has also been implicated in tumorigenesis. However, it is not known whether O-GlcNAcylation of NONO promotes cancer cell growth, and little is known about the effect of O-GlcNAcylation on the biological properties of NONO. This study identifies Thr440 as the primary NONO O-GlcNAcylation site and demonstrates its crucial role in the assembly of paraspeckles, an important subnuclear compartment that facilitates NONO-dependent transcriptional regulation in mammalian cells. We demonstrated that O-GlcNAcylation of NONO is required to maintain the expression of genes related to GO category “microtubule cytoskeleton organization involved in mitosis” and to suppress the expression of genes related to GO category “cellular response to type I interferon”. Moreover, stable depletion of NONO O-GlcNAcylation or NONO knockout significantly inhibited the growth of colon cancer cells. These findings highlight the importance of NONO and its O-GlcNAcylation status in modulating cell cycle progression, immune response, and tumorigenesis.
2024-06-01 | GSE262460 | GEO
Project description:We have previously shown that the Epstein-Barr virus (EBV) likely encodes hundreds of viral long non-coding RNAs (vlncRNAs) that are expressed during reactivation. Here we show that the EBV latency origin of replication (oriP) is transcribed bi-directionally during reactivation and that both leftward (oriPtLs) and rightward transcripts (oriPtRs) are largely localized in the nucleus. While the oriPtLs are most likely non-coding, at least some of the oriPtRs contain the BCRF1/vIL10 open reading frame. Nonetheless, oriPtR transcripts with long 5’UTRs may partially serve non-coding functions. Both oriPtL and oriPtR transcripts are expressed with late kinetics and their expression is inhibited by phosphonoacetic acid. RNA-seq analysis showed that oriPtLs and oriPtRs exhibited extensive “hyper-editing” at their Family of Repeat (FR) regions. RNA secondary structure prediction revealed that the FR region of both oriPtLs and oriPtRs may form large evolutionarily conserved and thermodynamically stable hairpins. The double-stranded RNA-binding protein and RNA-editing enzyme ADAR was found to bind to oriPtLs, likely facilitating editing of the FR hairpin. Further, the multifunctional paraspeckle protein, NONO, was found to bind to oriPt transcripts suggesting that oriPts interacts with the paraspeckle-based innate anti-viral immune pathway. Knock-down and ectopic expression of oriPtLs showed that it contributes to global viral lytic gene expression and viral DNA replication. Together, these results show that these new vlncRNAs interact with cellular innate immune pathways and that they help facilitate progression of the viral lytic cascade. RNA-seq analysis for oriPtL knockdown and overexpression experiments
2015-05-21 | E-GEOD-68122 | biostudies-arrayexpress
Project description:Vascular calcification is an important risk factor for the mortality and morbidity in chronic kidney disease (CKD). Unfortunately, until now there is no certain medication targeting vascular calcification in CKD. In this study, we explored the inhibitory effect of celastrol on high calcium-induced vascular calcification and the underlying molecular mechanisms. Cell proliferation assay showed that celastrol inhibited aortic valve interstitial cell (VIC) and vascular smooth muscle cell (VSMC) proliferation when its concentration was higher than 0.6 μmol/L. 0.8 μmol/L celastrol inhibited the expression of osteogenic genes and calcium deposition induced by high-calcium medium in both AVICs and VSMCs. In mouse vascular calcification model induced by adenine combined with vitamin D, alizarin red and immunostaining showed that celastrol inhibited pro-calcification gene expression and calcium deposition in aortic wall and aortic valve tissues. At the molecular level, celastrol inhibited the increase of BMP2, phosphorylated Smad1/5 (p-Smad1/5) and non-phosphorylated β-catenin (n-p-β-catenin) induced by high-calcium medium both in vitro and in vivo. Also, BMP2 overexpression reversed the anti-calcification effects of celastrol by recovering the decrease of p-Smad1/5 and n-p-β-catenin. Furthermore, celastrol prevented the up-regulation of BMPRII and down-regulation of Smad6 induced by high calcium, and this protectory effect can be abolished by BMP2 overexpression. In conclusion, our data for the first time demonstrate that celastrol attenuates high calcium-induced arterial and valvular calcification by inhibiting BMP2/Smad1/5 signalling, which may provide a novel therapeutic strategy for arterial and valvular calcification in patients with CKD.
| S-EPMC7686965 | biostudies-literature
Project description:MUC1-C subunit plays an essential role in regulating NEAT1 expression. MUC1-C activates the NEAT1 gene with induction of the NEAT1_1 and NEAT1_2 isoforms by NF-kB- and MYC-mediated mechanisms. MUC1-C/MYC signaling also induces expression of the SFPQ, NONO and FUS RNA binding proteins (RBPs) that associate with NEAT1_2 and are necessary for paraspeckle formation.
2024-04-08 | GSE247441 | GEO
Project description:O-GlcNAcylation of NONO is Critical for Paraspeckle Component Assembly and Contributes to Tumorigenesis
| PRJNA1091922 | ENA
Project description:Identifying causes of sporadic intellectual disability remains a considerable medical challenge. Here, we demonstrate that null mutations in the NONO gene, a member of the Drosophila Behavior Human Splicing (DBHS) protein family, are a novel cause of X-linked syndromic intellectual disability. Comparing humans to Nono-deficient mice revealed related behavioral and craniofacial anomalies, as well as global transcriptional dysregulation. Nono-deficient mice also showed deregulation of a large number of synaptic transcripts, causing a disorganization of inhibitory synapses, with impaired postsynaptic scaffolding of gephyrin. Alteration of gephyrin clustering could be rescued by over-expression of Gabra2 in NONO-compromised neurons. These findings link NONO to intellectual disability and first highlight the key role of DBHS proteins in functional organization of GABAergic synapses.
2015-09-02 | E-MTAB-2895 | biostudies-arrayexpress
Project description:Identifying causes of sporadic intellectual disability remains a considerable medical challenge. Here, we demonstrate that null mutations in the NONO gene, a member of the Drosophila Behavior Human Splicing (DBHS) protein family, are a novel cause of X-linked syndromic intellectual disability. Comparing humans to Nono-deficient mice revealed related behavioral and craniofacial anomalies, as well as global transcriptional dysregulation. Nono-deficient mice also showed deregulation of a large number of synaptic transcripts, causing a disorganization of inhibitory synapses, with impaired postsynaptic scaffolding of gephyrin. Alteration of gephyrin clustering could be rescued by over-expression of Gabra2 in NONO-compromised neurons. These findings link NONO to intellectual disability and first highlight the key role of DBHS proteins in functional organization of GABAergic synapses.
2015-09-02 | E-MTAB-2894 | biostudies-arrayexpress