A5070253632- RNA modifications and cancer
- RNA Research and Splicing
- Cancer-related molecular mechanisms research
- RNA and protein synthesis mechanisms
- Cytokine Signaling Pathways and Interactions
- Epigenetics and DNA Methylation
- Galectins and Cancer Biology
- Cancer-related gene regulation
- Phagocytosis and Immune Regulation
- Nanoplatforms for cancer theranostics
- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- Erythrocyte Function and Pathophysiology
- Immune Cell Function and Interaction
- Helicobacter pylori-related gastroenterology studies
- Plant Micronutrient Interactions and Effects
- interferon and immune responses
- Immune Response and Inflammation
- Eosinophilic Esophagitis
- Circular RNAs in diseases
- Bacterial Genetics and Biotechnology
- Viral Infections and Vectors
- Pulmonary Hypertension Research and Treatments
- RNA regulation and disease
- Cardiac Fibrosis and Remodeling
Kyoto University
2013-2024
Japan Agency for Medical Research and Development
2017-2018
Infrafrontier
2017
Background: Pulmonary arterial hypertension (PAH) is a type of pulmonary (PH) characterized by obliterative vascular remodeling, resulting in right-sided heart failure. Although the pathogenesis PAH not fully understood, inflammatory responses and cytokines have been shown to be associated with PAH, particular, connective tissue disease-PAH. In this sense, Regnase-1, an RNase that regulates mRNAs encoding genes related immune reactions, was investigated relation PH. Methods: We first...
Iron metabolism is regulated by transcriptional and post-transcriptional mechanisms. The mRNA of the iron-controlling gene, transferrin receptor 1 (TfR1), has long been believed to be negatively a yet-unidentified endonuclease. Here, we show that endonuclease Regnase-1 critical for degradation mRNAs involved in iron vivo. First, demonstrate promotes TfR1 decay. Next, Regnase-1-/- mice suffer from severe deficiency anemia, although hepcidin expression downregulated. anemia induced defect...
Abstract During erythroid differentiation, the maintenance of genome integrity is key for success multiple rounds cell division. However, molecular mechanisms coordinating expression DNA repair machinery in progenitors are poorly understood. Here, we discover that an RNA N 6 -methyladenosine (m A) methyltransferase, METTL16, plays essential role proper erythropoiesis by safeguarding via control DNA-repair-related genes. METTL16-deficient erythroblasts exhibit defective differentiation...
Abstract Regnase-1 and Roquin are RNA binding proteins that essential for degradation of inflammatory mRNAs maintenance immune homeostasis. Although deficiency either the leads to enhanced T cell activation, their functional relationship in cells has yet be clarified because lethality upon mutation both Roquin. By using a conditional allele, we show mutations massive lymphocyte activation. In contrast, or affected activation lesser extent than double mutation, indicating function...
Regnase-1 is an RNase critical for post-transcriptional control of pulmonary immune homeostasis in mice by degrading immune-related mRNAs. However, little known about the cell types controls lung, and its relevance to human diseases. Regnase-1-dependent changes lung were examined a competitive bone marrow transfer mouse model, group 2 innate lymphoid cells (ILC2s) identified. Then associations between ILC2s diseases investigated transcriptome analysis bleomycin-induced fibrosis model. The...
Abstract Inflammation orchestrates a finely balanced process crucial for microorganism elimination and tissue injury protection. A multitude of immune non-immune cells, alongside various proinflammatory cytokines chemokines, collectively regulate this response. Central to regulation is post-transcriptional control, governing gene expression at the mRNA level. RNA-binding proteins such as tristetraprolin, Roquin, Regnase family, along with RNA modifications, intricately dictate decay pivotal...
Regnase-1 is an ribonuclease that plays essential roles in restricting inflammation through degrading messenger RNAs (mRNAs) involved immune reactions via the recognition of stem-loop (SL) structures 3' untranslated regions (3'UTRs). Dysregulated expression associated with pathogenesis inflammatory and autoimmune diseases mice humans. Here, we developed a therapeutic strategy to suppress responses by blocking self-regulation, which was mediated simultaneous use two antisense...
Inhaled pathogens including Pseudomonas aeruginosa initially encounter airway epithelial cells (AECs), which are poised to evoke cell-intrinsic innate defense, affecting second tier of hematopoietic cell-mediated immune reaction. However, it is largely unknown how pulmonary responses mediated by a variety coordinated. Here we show that Regnase-1, an endoribonuclease expressed in AECs and cells, plays essential role coordinating adaptive immunity against P. infection. Intratracheal treatment...
The lipid mediator sphingosine 1-phosphate (S1P) regulates a wide range of cellular activities, including vascular maturation, angiogenesis, and immune-cell trafficking. Among the five known receptors for S1P (S1PR1-S1PR5), S1PR1 is critical regulator lymphocyte trafficking: its signaling required egress from lymphoid organs, while down-modulation by agonist-induced internalization prerequisite entry into organs bloodstream. Despite importance down-regulation in determining behavior,...
Abstract The ATP-dependent RNA helicase UPF1 plays a crucial role in various mRNA degradation pathways, most importantly nonsense-mediated decay (NMD). Here, we show that is upregulated during the early stages of B cell development and important for bone marrow. B-cell-specific Upf1 deletion mice severely impedes to late LPre-B transition, which V H -D J recombination occurs at Igh gene. Furthermore, indispensable recombination, without affecting D -J recombination. Intriguingly, genetic...
Toll-like receptor (TLR) stimulation induces glycolysis and the production of mitochondrial reactive oxygen species (ROS), both which are critical for inflammatory responses in macrophages. Here, we demonstrated that cyclin J, a TLR-inducible member family, reduced cytokine macrophages by coordinately controlling functions. Cyclin J interacted with cyclin-dependent kinases (CDKs), increased phosphorylation subset CDK substrates, including transcription factor FoxK1 GTPase Drp1. J–dependent...
Post-transcriptional regulation constitutes an important mechanism for governing gene expression across diverse biological processes.1 It is now appreciated that multiple types of methylation in mRNA provide post-transcriptional to control fates. N6-methyladenosine (m6A) one the most prevalent internal RNA modifications.2 m6A involved various aspects regulation, such as decay, translation and splicing. Accumulating evidence has shown controls numerous processes, cell development, immune...
Diffuse alveolar hemorrhage (DAH) is one of the serious complications associated with systemic lupus erythematosus, an autoimmune disease whose pathogenesis involves type I IFNs and cytokines. Here, we show that TANK, a negative regulator NF-κB signaling via suppression TRAF6 ubiquitination, critical for amelioration fatal DAH caused by lung vascular endothelial cell death in mouse model erythematosus. The development absence TANK mediated IFN signaling, but not IL-6. We further uncover...
Abstract Codon bias has been implicated as one of the major factors contributing to mRNA stability in yeast. However, effects codon-bias on remain unclear humans. Here we show that human cells possess a mechanism modulate RNA through unique codon different from Bioinformatics analysis showed codons could be clustered into two distinct groups – with G or C at third base position (GC3) and either A T (AT3); former stabilizing while latter destabilizing mRNA. Quantification increased GC3...