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Biomolecules Feb 2017To date, about 90 post-transcriptional modifications have been reported in tRNA expanding their chemical and functional diversity. Methylation is the most frequent... (Review)
Review
To date, about 90 post-transcriptional modifications have been reported in tRNA expanding their chemical and functional diversity. Methylation is the most frequent post-transcriptional tRNA modification that can occur on almost all nitrogen sites of the nucleobases, on the C5 atom of pyrimidines, on the C2 and C8 atoms of adenosine and, additionally, on the oxygen of the ribose 2'-OH. The methylation on the N1 atom of adenosine to form 1-methyladenosine (m1A) has been identified at nucleotide position 9, 14, 22, 57, and 58 in different tRNAs. In some cases, these modifications have been shown to increase tRNA structural stability and induce correct tRNA folding. This review provides an overview of the currently known m1A modifications, the different m1A modification sites, the biological role of each modification, and the enzyme responsible for each methylation in different species. The review further describes, in detail, two enzyme families responsible for formation of m1A at nucleotide position 9 and 58 in tRNA with a focus on the tRNA binding, m1A mechanism, protein domain organisation and overall structures.
Topics: Adenosine; Animals; Enzymes; Humans; Methylation; Models, Molecular; RNA Processing, Post-Transcriptional; RNA, Transfer
PubMed: 28230814
DOI: 10.3390/biom7010020 -
Zhongguo Fei Ai Za Zhi = Chinese... Jul 2022Adenosine is a metabolite produced abundantly in the tumor microenvironment, dampening immune response in inflamed tissues via adenosine A2A receptor (A2AR) which is... (Review)
Review
Adenosine is a metabolite produced abundantly in the tumor microenvironment, dampening immune response in inflamed tissues via adenosine A2A receptor (A2AR) which is widely expressed on immune cells, inhibiting anti-tumor immune response accordingly. Therefore, blocking adenosine signaling pathway is of potential to promote anti-tumor immunity. This review briefly introduces adenosine signaling pathway, describes its role in regulating tumor immunity and highlights A2AR blockade in cancer therapy. Prospective anti-tumor activity of adenosine/A2AR inhibition has been revealed by preclinical data, and a number of clinical trials of A2AR antagonists are under way. Primary results from clinical trials suggest that A2AR antagonists are well tolerated in cancer patients and are effective both as monotherapy and in combination with other therapies. In the future, finding predictive biomarkers are critical to identify patients most likely to benefit from adenosine pathway blockade, and further researches are needed to rationally combine A2AR antagonists with other anti-tumor therapies. .
Topics: Adenosine; Adenosine A2 Receptor Antagonists; Humans; Lung Neoplasms; Receptor, Adenosine A2A; Tumor Microenvironment
PubMed: 35899442
DOI: 10.3779/j.issn.1009-3419.2022.102.24 -
Transcription Oct 2021RNA modifications are prevalent among all the classes of RNA, regulate diverse biological processes, and have emerged as a key regulatory mechanism in... (Review)
Review
RNA modifications are prevalent among all the classes of RNA, regulate diverse biological processes, and have emerged as a key regulatory mechanism in post-transcriptional control of gene expression. They are subjected to precise spatial and temporal control and shown to be critical for the maintenance of normal development and physiology. For example, mA modification of mRNA affects stability, recruitment of RNA binding protein (RBP), translation, and splicing. The deposition of m6A on the RNA happens co-transcriptionally, allowing the tight coupling between the transcription and RNA modification machinery. The mA modification is affected by transcriptional dynamics, but recent insights also suggest that mA machinery impacts transcription and chromatin signature.
Topics: Adenosine; Gene Expression Regulation; RNA; RNA Processing, Post-Transcriptional; RNA Splicing; RNA, Messenger
PubMed: 35380917
DOI: 10.1080/21541264.2022.2057177 -
Molecular Therapy : the Journal of the... Oct 2020Cardiovascular diseases (CVDs) remain the leading cause of death and disability worldwide, despite marked improvements in prevention, diagnosis, and early intervention.... (Review)
Review
Cardiovascular diseases (CVDs) remain the leading cause of death and disability worldwide, despite marked improvements in prevention, diagnosis, and early intervention. There is an urgent need to discover more effective therapeutic strategies, which would be facilitated by a more in-depth understanding of CVDs and their underlying molecular mechanisms. Recent advances in knowledge about epigenetic mechanisms, especially RNA methylation, have revealed a close relationship between epigenetic modifications and CVDs and have brought to potential novel targets for diagnosis and treatment. Here, we provide a review of recent studies exploring RNA N-methyladenosine (mA) modification, with particular emphasis on its role in CVDs, such as coronary heart disease, hypertension, cardiac hypertrophy, and heart failure. We also introduce the "life cycle" of mA and its dominant function in several biological processes. Finally, we highlight the prospects of treatment based on interfering with mA, which could have a transformative effect on clinical medicine.
Topics: Adenosine; Cardiovascular Diseases; Disease Susceptibility; Epigenesis, Genetic; Gene Expression Regulation; Humans; Methylation; Molecular Targeted Therapy; RNA
PubMed: 32910911
DOI: 10.1016/j.ymthe.2020.08.010 -
Cell Communication and Signaling : CCS Sep 2022N6-methyl-adenosine (mA) is the most prevalent modification on mRNAs and long noncoding RNAs (lnRNAs) in higher eukaryotes. Modulation of mA relies on mA writers,... (Review)
Review
N6-methyl-adenosine (mA) is the most prevalent modification on mRNAs and long noncoding RNAs (lnRNAs) in higher eukaryotes. Modulation of mA relies on mA writers, erasers and readers. mA modification contributes to diverse fundamental biological functions at the molecular, cellular, and physiological levels. The dysregulation of mA modification has been implicated in various human diseases. Thus, mA modification has now become a research hotspot for its potential therapeutic applications in the treatment of various cancers and diseases. The immune system is essential to provide defense against infections and cancers. This review summarizes the current knowledge about the roles of mA in regulating immune cell functions and immune responses. Video abstract.
Topics: Adenosine; Humans; Methylation; Methyltransferases; Neoplasms
PubMed: 36085064
DOI: 10.1186/s12964-022-00939-8 -
British Journal of Pharmacology Jul 2017Adenosine is an endogenous ubiquitous purine nucleoside, which is increased by hypoxia, ischaemia and tissue damage and mediates a number of physiopathological effects... (Review)
Review
Adenosine is an endogenous ubiquitous purine nucleoside, which is increased by hypoxia, ischaemia and tissue damage and mediates a number of physiopathological effects by interacting with four GPCRs, identified as A , A , A and A . Physiological and acutely increased adenosine is mostly associated with beneficial effects that include vasodilatation and a decrease in inflammation. In contrast, chronic overproduction of adenosine occurs in important pathological states, where long-lasting increases in the nucleoside levels are responsible for the bad side of adenosine associated with chronic inflammation, fibrosis and organ damage. In this review, we describe and critically discuss the pathological overproduction of adenosine and analyse when, where and how adenosine exerts its detrimental effects throughout the body.
Topics: Adenosine; Animals; Humans; Neurodegenerative Diseases
PubMed: 28252203
DOI: 10.1111/bph.13763 -
Cell Proliferation Jan 2022N6-Methyladenosine (m6A) is considered the most common and endogenous modification of eukaryotic RNAs. Highly conserved in many species, m6A regulates RNA metabolism,... (Review)
Review
N6-Methyladenosine (m6A) is considered the most common and endogenous modification of eukaryotic RNAs. Highly conserved in many species, m6A regulates RNA metabolism, cell differentiation, cell circadian rhythm, and cell cycle; it also responds to endogenous and exogenous stimuli and is associated with the development of tumors. The m6A methyltransferase complex (MTC) regulates the m6A modification of transcripts and involves two components, methyltransferase-like enzyme 3 (METTL3) and methyltransferase-like enzyme 14 (METTL14), and other auxiliary regulatory distinct components. Though with no catalytic effect, METTL14 serves as an RNA-binding scaffold in MTC, promotes RNA substrate recognition, activates, and escalates the catalytic capability of METTL3, thus accounting for a pivotal member of the complex. It was reported that METTL14 regulates tumor proliferation, metastasis, and self-renewal, and plays a part in tumorigenesis, tumor progression, and other processes. The present work is a review of the role of METTL14 both as a tumor suppressor and a tumor promoter in the oncogenesis and progression of various tumors, as well as the potential molecular mechanisms.
Topics: Adenosine; Animals; Genes, Tumor Suppressor; Humans; Methyltransferases; Neoplasms; Oncogenes; RNA
PubMed: 34904301
DOI: 10.1111/cpr.13168 -
Postepy Biochemii Jun 2019Cytokinins are a group of plant hormones which play an important role in plant growth and development. They produce various effects when applied to intact plants. They... (Review)
Review
Cytokinins are a group of plant hormones which play an important role in plant growth and development. They produce various effects when applied to intact plants. They particularly stimulate protein synthesis and participate in cell cycle control. First discovered cytokinin was N6-furfuryladenine (kinetin). It is a strong inhibitor of proteins and nucleic acids oxidation in vitro and in vivo. Both kinetin and its ribosides (N6-furfuryladenosine, kinetin riboside) as natural compounds occur in the milk of coconuts on the nanomole level. Kinetin riboside selectively inhibits the proliferation of cancer cells and induce their apoptosis. This review focuses on the kinetin riboside occurrence, and primarily on its metabolism, and biological activity.
Topics: Adenosine; Apoptosis; Kinetin; Neoplasms; Plant Growth Regulators; Plants
PubMed: 31642649
DOI: 10.18388/pb.2019_265 -
Genes May 2022-methyladenosine (mA) is a prevalent and reversible post-transcriptional RNA modification that decorates tRNA, rRNA and mRNA. Recent studies based on technical advances... (Review)
Review
-methyladenosine (mA) is a prevalent and reversible post-transcriptional RNA modification that decorates tRNA, rRNA and mRNA. Recent studies based on technical advances in analytical chemistry and high-throughput sequencing methods have revealed the crucial roles of mA RNA modification in gene regulation and biological processes. In this review, we focus on progress in the study of mA methyltransferases, mA demethylases and mA-dependent RNA-binding proteins and highlight the biological mechanisms and functions of mA RNA modification, as well as its association with human disease. We also summarize the current understanding of detection approaches for mA RNA modification.
Topics: Adenosine; Gene Expression Regulation; Humans; Methylation; RNA Processing, Post-Transcriptional; RNA, Messenger
PubMed: 35627295
DOI: 10.3390/genes13050910 -
Cell Death & Disease Jun 2020Ischemia-reperfusion (I/R) injury is common during surgery and often results in organ dysfunction. The mechanisms of I/R injury are complex, diverse, and not well... (Review)
Review
Ischemia-reperfusion (I/R) injury is common during surgery and often results in organ dysfunction. The mechanisms of I/R injury are complex, diverse, and not well understood. RNA methylation is a novel epigenetic modification that is involved in the regulation of various biological processes, such as immunity, response to DNA damage, tumorigenesis, metastasis, stem cell renewal, fat differentiation, circadian rhythms, cell development and differentiation, and cell division. Research on RNA modifications, specifically N6-methyladenosine (mA), have confirmed that they are involved in the regulation of organ I/R injury. In this review, we summarized current understanding of the regulatory roles and significance of mA RNA methylation in I/R injury in different organs.
Topics: Adenosine; Animals; Epigenesis, Genetic; Humans; Methylation; Organ Specificity; Reperfusion Injury; Signal Transduction
PubMed: 32581252
DOI: 10.1038/s41419-020-2686-7