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Journal of the American Chemical Society Nov 2023Queuosine is one of the most complex hypermodified RNA nucleosides found in the Wobble position of tRNAs. In addition to Queuosine itself, several further modified...
Queuosine is one of the most complex hypermodified RNA nucleosides found in the Wobble position of tRNAs. In addition to Queuosine itself, several further modified derivatives are known, where the cyclopentene ring structure is additionally modified by a galactosyl-, a mannosyl-, or a glutamyl-residue. While sugar-modified Queuosine derivatives are found in the tRNAs of vertebrates, glutamylated Queuosine (gluQ) is only known in bacteria. The exact structure of gluQ, particularly with respect to how and where the glutamyl side chain is connected to the Queuosine cyclopentene side chain, is unknown. Here we report the first synthesis of gluQ and, using UHPLC-MS-injection and NMR studies, we show that the isolated natural gluQ is the α-allyl-connected gluQ compound.
Topics: Animals; Nucleoside Q; RNA, Transfer; Bacteria; Cyclopentanes
PubMed: 37967838
DOI: 10.1021/jacs.3c10075 -
Purinergic Signalling Jun 2022Quorum sensing indicates a communication process between bacteria based on a coordinate variation in gene expression aimed at coordinating a collective comportment...
Quorum sensing indicates a communication process between bacteria based on a coordinate variation in gene expression aimed at coordinating a collective comportment related to the bacterial population density. Increasing pieces of evidence pointed out that a quorum-sensing system can be a regulatory program also used in the immune field to organize the density of the various immune cell populations and to calibrate their responses. In particular, such equilibrium is achieved by the ability of immune cells to perceive the density of their own populations or those of other cells in their environment, through the release of several mediators able to finely shape the cell density via coordinated changes in gene expression and protein signaling. In this regard, adenosine displays the typical characteristics of a mediator involved in the regulation of quorum sensing, thus suggesting a putative role of this nucleoside in shaping the balance between diverse immune cell populations.
Topics: Adenosine; Quorum Sensing; Signal Transduction
PubMed: 35501535
DOI: 10.1007/s11302-022-09866-2 -
Cells Feb 2024At the intestinal front, several lines of defense are in place to resist infection and injury, the mucus layer, gut microbiome and strong epithelial junctions, to name a... (Review)
Review
At the intestinal front, several lines of defense are in place to resist infection and injury, the mucus layer, gut microbiome and strong epithelial junctions, to name a few. Their collaboration creates a resilient barrier. In intestinal disorders, such as inflammatory bowel disease (IBD), barrier function is compromised, which results in rampant inflammation and tissue injury. In response to the destruction, the intestinal epithelium releases adenosine, a small but powerful nucleoside that functions as an alarm signal. Amidst the chaos of inflammation, adenosine aims to restore order. Within the scope of its effects is the ability to regulate intestinal epithelial barrier integrity. This review aims to define the contributions of adenosine to mucus production, microbiome-dependent barrier protection, tight junction dynamics, chloride secretion and acid-base balance to reinforce its importance in the intestinal epithelial barrier.
Topics: Humans; Adenosine; Inflammatory Bowel Diseases; Inflammation; Intestinal Mucosa
PubMed: 38474346
DOI: 10.3390/cells13050381 -
Zhong Nan Da Xue Xue Bao. Yi Xue Ban =... Aug 2022N6-methyladenosine (m6A) is the predominant post-transcriptional modification for eukaryotic mRNA. It's regulated by methyltransferases, demethylases, and m6A binding...
N6-methyladenosine (m6A) is the predominant post-transcriptional modification for eukaryotic mRNA. It's regulated by methyltransferases, demethylases, and m6A binding proteins, and plays an important role in regulating splicing, translation, and degradation of mRNA. Skin diseases, especially immune skin diseases and skin tumors, have a complicated pathogenesis and are refractory to treatment, seriously affecting the patient quality of life. Recent studies have revealed that m6A and its regulatory proteins can affect the development of numerous skin diseases. The m6A modification was found to be involved in skin accessory development, including hair follicle and sweat gland formation. The level of m6A modification was significantly altered in a variety of skin diseases including melanoma, cutaneous squamous cell carcinoma, Merkel cell carcinoma, and psoriasis, and affected a variety of biological processes including cell proliferation and differentiation migration. The m6A and its regulatory proteins may become potential molecular markers or therapeutic targets for skin diseases, and have promising clinical applications in early diagnosis, efficacy determination, prognosis prediction, and gene therapy of skin diseases.
Topics: Adenosine; Carcinoma, Squamous Cell; Humans; Quality of Life; RNA, Messenger; Skin Neoplasms
PubMed: 36097784
DOI: 10.11817/j.issn.1672-7347.2022.210332 -
Cancer Gene Therapy Jun 2024RNA modification, especially N6-methyladenosine, 5-methylcytosine, and N7-methylguanosine methylation, participates in the occurrence and progression of cancer through... (Review)
Review
RNA modification, especially N6-methyladenosine, 5-methylcytosine, and N7-methylguanosine methylation, participates in the occurrence and progression of cancer through multiple pathways. The function and expression of these epigenetic regulators have gradually become a hot topic in cancer research. Mutation and regulation of noncoding RNA, especially lncRNA, play a major role in cancer. Generally, lncRNAs exert tumor-suppressive or oncogenic functions and its dysregulation can promote tumor occurrence and metastasis. In this review, we summarize N6-methyladenosine, 5-methylcytosine, and N7-methylguanosine modifications in lncRNAs. Furthermore, we discuss the relationship between epigenetic RNA modification and lncRNA interaction and cancer progression in various cancers. Therefore, this review gives a comprehensive understanding of the mechanisms by which RNA modification affects the progression of various cancers by regulating lncRNAs, which may shed new light on cancer research and provide new insights into cancer therapy.
Topics: Humans; Neoplasms; RNA, Long Noncoding; Epigenesis, Genetic; Gene Expression Regulation, Neoplastic; Adenosine; Animals; RNA Processing, Post-Transcriptional
PubMed: 38351139
DOI: 10.1038/s41417-024-00734-2 -
International Journal of Molecular... May 2022Epitranscriptomic modifications can affect every aspect of RNA biology, including stability, transport, splicing, and translation, participate in global intracellular... (Review)
Review
Epitranscriptomic modifications can affect every aspect of RNA biology, including stability, transport, splicing, and translation, participate in global intracellular mRNA metabolism, and regulate gene expression and a variety of biological processes. N6-methyladenosine (m6A) as the most prevalent modification contributes to normal embryonic brain development and memory formation. However, changes in the level of m6A modification and the expression of its related proteins cause abnormal nervous system functions, including brain tissue development retardation, axon regeneration disorders, memory changes, and neural stem cell renewal and differentiation disorders. Recent studies have revealed that m6A modification and its related proteins play key roles in the development of various neuropsychiatric disorders, such as depression, Alzheimer's disease, and Parkinson's disease. In this review, we summarize the research progresses of the m6A modification regulation mechanism in the central nervous system and discuss the effects of gene expression regulation mediated by m6A modification on the biological functions of the neuropsychiatric disorders, thereby providing some insight into new research targets and treatment directions for human diseases.
Topics: Adenosine; Axons; Humans; Nerve Regeneration; RNA
PubMed: 35682599
DOI: 10.3390/ijms23115922 -
Methods in Molecular Biology (Clifton,... 2021The conversion of adenosine to inosine (A to I) by RNA editing represents a common posttranscriptional mechanism for diversification of both the transcriptome and...
The conversion of adenosine to inosine (A to I) by RNA editing represents a common posttranscriptional mechanism for diversification of both the transcriptome and proteome, and is a part of the cellular response for innate immune tolerance. Due to its preferential base-pairing with cytosine (C), inosine (I) is recognized as guanosine (G) by reverse transcriptase, as well as the cellular splicing and translation machinery. A-to-I editing events appear as A-G discrepancies between genomic DNA and cDNA sequences. Molecular analyses of RNA editing have leveraged these nucleoside differences to quantify RNA editing in ensemble populations of RNA transcripts and within individual cDNAs using high-throughput sequencing or Sanger sequencing-derived analysis of electropherogram peak heights. Here, we briefly review and compare these methods of RNA editing quantification, as well as provide experimental protocols by which such analyses may be achieved.
Topics: Adenosine; DNA, Complementary; Genome, Human; High-Throughput Nucleotide Sequencing; Humans; Inosine; RNA Editing; Transcriptome
PubMed: 32729077
DOI: 10.1007/978-1-0716-0787-9_7 -
Journal of Medicine and Life Jun 2023Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. This study aimed to investigate the potential protective effect of...
Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. This study aimed to investigate the potential protective effect of the lungs in sepsis by modulating inflammatory and oxidative stress markers. Twenty-four adult male Swiss-albino mice, aged 8-12 weeks and weighing 20-30 g, were divided into four equal groups (n=6): sham (laparotomy only), CLP (laparotomy plus cecal ligation and puncture), vehicle (DMSO administered one hour before CLP), and Ticagrelor (50 mg/kg IP administered one hour before CLP). Tissue levels of pro-inflammatory and oxidative stress markers in the lung were assessed using ELISA. F2 isoprostane levels were significantly higher in the sepsis group (p<0.05) compared to the sham group, while Ticagrelor significantly decreased the inflammatory and oxidative stress markers compared to the sepsis group. All mice in the sepsis group had considerable (p=0.05) lung tissue damage, but Ticagrelor considerably decreased lung tissue injury (p=0.05). Furthermore, Ticagrelor was found to reduce tissue cytokine levels of the lung (IL-1, TNF a, IL-6, F2 isoprostane, GPR 17, MIF) in male mice during CLP-induced polymicrobial sepsis by modulation of pro-inflammatory and oxidative stress cascade signaling pathways.
Topics: Male; Animals; Mice; Endotoxemia; F2-Isoprostanes; Ticagrelor; Sepsis; Lung
PubMed: 37675176
DOI: 10.25122/jml-2022-0308 -
Cell Death & Disease Mar 2021The innate and adaptive immune cells have complex signaling pathways for sensing and initiating immune responses against disease. These pathways are interrupted at... (Review)
Review
The innate and adaptive immune cells have complex signaling pathways for sensing and initiating immune responses against disease. These pathways are interrupted at different levels to occur immune evasion, including by N6-methyladenosine (m6A) modification. In this review, we discuss studies revealing the immune evasion mechanism by m6A modification, which underlies the retouching of these signaling networks and the rapid tolerance of innate and adaptive immune molecules during disease. We also focus on the functions of m6A in main chemokines regulation, and their roles in promotive and suppressive immune cell recruitment. We then discuss some of the current challenges in the field and describe future directions for the immunological mechanisms of m6A modification.
Topics: Adenosine; Disease Progression; Humans; Immune Evasion; RNA
PubMed: 33741904
DOI: 10.1038/s41419-021-03585-z -
Journal of Cardiothoracic Surgery Dec 2022Despite the rise in morbidity and mortality associated with vascular diseases, the underlying pathophysiological molecular mechanisms are still unclear. RNA... (Review)
Review
Despite the rise in morbidity and mortality associated with vascular diseases, the underlying pathophysiological molecular mechanisms are still unclear. RNA N6-methyladenosine modification, as the most common cellular mechanism of RNA regulation, participates in a variety of biological functions and plays an important role in epigenetics. A large amount of evidence shows that RNA N6-methyladenosine modifications play a key role in the morbidity caused by vascular diseases. Further research on the relationship between RNA N6-methyladenosine modifications and vascular diseases is necessary to understand disease mechanisms at the gene level and to provide new tools for diagnosis and treatment. In this study, we summarize the currently available data on RNA N6-methyladenosine modifications in vascular diseases, addressing four aspects: the cellular regulatory system of N6-methyladenosine methylation, N6-methyladenosine modifications in risk factors for vascular disease, N6-methyladenosine modifications in vascular diseases, and techniques for the detection of N6-methyladenosine-methylated RNA.
Topics: Humans; Methylation; RNA; Adenosine; Vascular Diseases
PubMed: 36536469
DOI: 10.1186/s13019-022-02077-1