Diabetes mellitus(DM)and obesity have become two of the most prevalent and challenging diseases worldwide,with increasing incidence and serious *** studies have shown that noncoding rna(ncrna)and epigenetic regulation...
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Diabetes mellitus(DM)and obesity have become two of the most prevalent and challenging diseases worldwide,with increasing incidence and serious *** studies have shown that noncoding rna(ncrna)and epigenetic regulation play crucial roles in the pathogenesis of DM complicated by *** of the involvement of ncrna and epigenetic regulation in the pathogenesis of diabetes with obesity has opened new avenues of *** these mechanisms with small molecules or rna-based therapies may provide a more precise and effective approach to diabetes treatment than traditional *** this review,we discuss the molecular mechanisms of ncrna and epigenetic regulation and their potential therapeutic targets,and the research prospects for DM complicated with obesity.
Background and objectives: The insulin-like growth factor (IGF) signaling system is a major arena of intragenomic conflict over embryonic growth between imprinted genes of maternal and paternal origin and the IGF type...
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Background and objectives: The insulin-like growth factor (IGF) signaling system is a major arena of intragenomic conflict over embryonic growth between imprinted genes of maternal and paternal origin and the IGF type 1 receptor (IGF1R) promotes proliferation of many human cancers. The 3'-untranslated region (3'-UTR) of the mouse Igf1r mrna is targeted by miR-675-3p derived from the imprinted H19 long noncoding rna. We undertook a comparative sequence analysis of vertebrate IGF1R 3'-UTRs to determine the evolutionary history of miR-675 target sequences and to identify conserved features that are likely to be involved in post-transcriptional regulation of IGF1R translation. Methodology: Sequences of IGF1R 3'-UTRs were obtained from public databases and analyzed using publicly available algorithms. Results: A very long 3'-UTR is a conserved feature of vertebrate IGF1R mrnas. We found that some ancient micrornas, such as let-7 and mir-182, have predicted binding sites that are conserved between cartilaginous fish and mammals. One very conserved region is targeted by multiple, maternally expressed imprinted micrornas that appear to have evolved more recently than the targeted sequences. Conclusions and implications: The conserved structures we identify in the IGF1R 3'-UTR are strong candidates for regulating cell proliferation during development and carcinogenesis. These conserved structures are now targeted by multiple imprinted micrornas. These observations emphasize the central importance of IGF signaling pathways in the mediation of intragenomic conflicts over embryonic growth and identify possible targets for therapeutic interventions in cancer.
It has long been assumed that mirnas can only target protein-coding mrnas in the cytoplasm. Recent studies, however, reveal mirnas are also transported from the cytoplasm to the nucleus, where they function in a nonca...
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It has long been assumed that mirnas can only target protein-coding mrnas in the cytoplasm. Recent studies, however, reveal mirnas are also transported from the cytoplasm to the nucleus, where they function in a noncanonical manner to regulate noncoding rnas. Here, we highlight the working model of these noncanonical mirnas.
noncoding rnas (ncrnas) have important functional roles in biological processes and have become a central research interest in modern molecular biology. However, how to find ncrna attracts much more attention since nc...
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Despite increasing interest in the biology of noncoding rnas (ncrnas), few functions have been uncovered for viral ncrnas in vivo. In their recent article in mSphere, Feldman and colleagues [E. R. Feldman et al., mSph...
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Despite increasing interest in the biology of noncoding rnas (ncrnas), few functions have been uncovered for viral ncrnas in vivo. In their recent article in mSphere, Feldman and colleagues [E. R. Feldman et al., mSphere 1(2): e00105-15, 2016, doi: 10.1128/mSphere. 00105-15] demonstrate a highly specific activity of a gammaherpesviral ncrna in viral dissemination and establishment of latent infection. Their work highlights several interesting features that should be informative to future studies of viral ncrna.
rnaz is a widely used software package for de novo detection of structured noncoding rnas in comparative genomics data. Four years of experience have not only demonstrated the applicability of the approach, but also h...
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ISBN:
(纸本)9789814295291
rnaz is a widely used software package for de novo detection of structured noncoding rnas in comparative genomics data. Four years of experience have not only demonstrated the applicability of the approach, but also helped us to identify limitations of the current implementation. rnaz 2.0 provides significant improvements in two respects: (1) The accuracy is increased by the systematic use of dinucleotide models. (2) Technical limitations of the previous version, such as the inability to handle alignments with more than six sequences, are overcome by increased training data and the usage of an entropy measure to represent sequence similarities. rnaz 2.0 shows a significantly lower false discovery rate on a dinucleotide background model than the previous version. Separate models for structural alignments provide an additional way to increase the predictive power. rnaz is open source software and can be obtained free of charge at: http://***-wash/rnaz/
Given the important role of the blood-brain barrier (BBB) in the central nervous system (CNS), increasing studies have been carried out to determine how the structural and functional integrity of the BBB impacts the p...
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Given the important role of the blood-brain barrier (BBB) in the central nervous system (CNS), increasing studies have been carried out to determine how the structural and functional integrity of the BBB impacts the pathogenesis of CNS diseases such as stroke, traumatic brain injuries (TBIs), and gliomas. Emerging studies have revealed that noncoding rnas (ncrnas) help to maintain the integrity and permeability of the BBB, thereby mediating CNS homeostasis. This review summarizes recent studies that focus on the effects of ncrnas on the BBB in CNS diseases, including regulating the biological processes of inflammation, necrosis, and apoptosis of cells, affecting the translational dysfunction of proteins and regulating tight junctions (TJs). A comprehensive and detailed understanding of the interaction between ncrnas and the BBB will lay a solid foundation for the development of early diagnostic methods and effective treatments for CNS diseases.
Naïve CD4+ T cells polarize into many varied CD4+ T-helper (TH) cell subsets depending on the cytokine milieu present during T cell receptor stimulation. Each T cell subset produces a unique cytokine profile to d...
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Naïve CD4+ T cells polarize into many varied CD4+ T-helper (TH) cell subsets depending on the cytokine milieu present during T cell receptor stimulation. Each T cell subset produces a unique cytokine profile to defend against varied pathogens. The polarization of each T cell subset is regulated by unique transcription factors and noncoding elements to induce cytokine expression. The research detailed identifies a noncoding rna, GATA3-AS1, which is necessary for the expression of GATA3 and TH2 cell polarization. Furthermore, we describe the repression of IFN-γ by super-enhancer disruption via bromodomain inhibitor JQ1. Our results lend novel insight into the regulation of hallmark genes by noncoding elements in T-helper cell polarization.
Long noncoding rnas (lncrnas) are being realized as important players in gene regulation and their misregulation has been considered as one of the underlying causes for tumor initiation and progression in many human p...
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Long noncoding rnas (lncrnas) are being realized as important players in gene regulation and their misregulation has been considered as one of the underlying causes for tumor initiation and progression in many human pathologies. In the current thesis, I have addressed the functional role of lncrnas in development and disease model systems. Genomic imprinting is an epigenetic phenomenon by which subset of genes are expressed in a parent of origin-specific manner. The Kcnq1 imprinted locus is epigenetically regulated by Kcnq1ot1 lncrna. Deletion of an 890bp region at the 5' end of Kcnq1ot1 in mouse resulted in the loss of silencing of neighboring ubiqui-tously imprinted genes (UIGs). In addition, we observed loss of DNA methylation at the UIG promoters. We have shown that Kcnq1ot1 rna establishes CpG methylation by interacting with DNMT1. To explore the stability of lncrna mediated silencing pathways, we have conditionally deleted Kcnq1ot1 in the mouse in a stage and tissue-specific manner. We have shown that Kcnq1ot1 is continuously required for maintaining the silencing of UIGs, whereas the silencing of the placental im-printed genes is maintained in an rna independent manner. To identify chromatin-associated lncrna (CARs) on a genome-wide scale, we purified rna from the sucrose gradient fractionated chromatin and subjected it to rna sequencing. Our study has identified 141 intronic and 74 long intergenic CARs. Characterization of one of the CARs revealed that it regulates the expression of neighboring genes in cis by modulating the chromatin structure. We have explored the functional role of lncrna in tumor progression and initiation by using pediatric neuroblastoma. By transcriptional profiling of low- and high-risk tumors, we have identified several lncrnas differentially expressed between these subtypes. We report an uncharacterized rna NBAT-1, expressed at lower levels in high-risk tumors relative to low- risk tumors. Using neuroblastoma cell culture system, we
The unique ability of the adult liver to regenerate after injury is the basis for efficient surgical resection and liver transplantation and provides solutions for the treatment of liver cancer and acute liver failure...
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The unique ability of the adult liver to regenerate after injury is the basis for efficient surgical resection and liver transplantation and provides solutions for the treatment of liver cancer and acute liver failure. Current success in surgical treatments could be enhanced by directed regulation of liver regeneration. A number of small molecules and growth factors have been tested in mice models to improve liver regeneration. noncoding ribonucleic acids (ncrna) are less studied regulators of various cellular processes. Here, the authors carefully review ncrna involved in liver regeneration and discuss molecular mechanisms and regulatory networks. These ncrnas modulate the expression of pro- and antiproliferative genes allowing to orchestrate precisely the proliferation of hepatocytes. The authors expect that ncrna will become new targets in liver regeneration due to recent progress in therapeutic nucleic acids. Among a large number of preclinical studies on ncrna, only a few entered clinical trials, and further studies are needed to uncover their potential as therapeutic targets.
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